Study No. 5221.06
TOXICTIY OF
IN
Performed for:
Triaajle institute
P.O. Box 12194
Triangle Park
North Carolina 27709
Revised Final Report
Hareh 21,
-------
-------
50272-101
REPORT DOCUMENTATION
PAGE
1. REPORT NO.
EPA/530-SW-88-027
3. Recipient's Accession No.
PB88-197496/AS
4, Title and Subtitle
Subchronic Toxicity of Ortho-Cresol in Sprague
Dawley Rats
5. Report Date
March 21, 1988
7. Author(s)
Dr. Dennis Dietz and Dr, L. Thomas Mulligan
8, Performing Organization Rep'- No.
9, Performing Organization Name and Address
Microbiological Associates, Inc.
5221 River Road - ™- ~ "
Bethesda, MD 20816
10. Project/Task/Work Unit No.
11. Contraet(C) or Grant(G) No.
-------
-------
Study No. 5221.06
SUBCHRQNIC TOXZCEEY OF OHIKXEESOL
IN SFKAGUE DAWIEY RATS
MAI Chemical No.: 23
Sponsor:
Sponsor
Representative:
Research Triangle Institute
P.O. BOX 12194
Research triangle Park
North Carolina 27709
Dr. Dennis D. Dietz
Testing Facility? Microbiological Associates Inc. (MBA)
5221 River Road
Bethesda, Mayland 20816
Initiation Date: September 16, 1985
Completion Date: December 18, 1985
L. Thomas wlligan, Tff.D.
study Director '
-------
-------
ACKNOWLEDGEMENT
This report 1s submitted in partial fulfillment of the requirements of Work
Assignment No. 35, EPA Contract No, 68-01-7075. This study was conducted by
Microbiological Associates, Incorporated as a subcontractor to Research Triangle
Institute (RTI).
Dr. Dennis Dietz, formerly of RTI, was the work assignment leader. Dr.
Reva Rubenstein of EPA was the work assignment manager and provided technical
direction and comment. Dr, Ambika Bathija, also of EPA, provided review
comments and direction on the finalization of the report.
-------
-------
Study No. 5221.06
TABLE "OF CONTENTS
Page
I. SUMMARY 1
II. INTRODUCTION......... 1
III. MATERIALS MD METHODS 1
A. Test Article. "......., 1
B. Animals.. 1
C. Experimental Design 2
D. Statistical Analyses. .................. 6
TV. RESULTS..... 6
A. Analyses and Stability of Dosage Form Preparations...... 6
B. Mortality/Clinical Observations, 6
C. Body Weight. 7
D. Food Consumption. 8
E. Clinical Pathology. 8
F. Ophthalmology...... 8
G. Organ Weights 9
H. Pathology .' ........ 9
V. DISCUSSION. 9
VI. PERSONNEL 10
VII. ARCHIVES ... 10
APPENDICES
APPENDIX A - TWO-WEEK KANGE-FM^G/EXPDORATORY STUDY
OF OKIHO-CKESOL IN SPRAGUE DAWLEY RATS ....... A-l
APPENDIX B - ANALYTICAL CHEMISTRY METHODOLOGY. B-l
APPENDIX C - CLINICAL PATHOLOGY METHODOLOGY C-l
APPENDIX D - INDIVIDUAL ANIMAL DATA. D-l
APPENDIX E - OPHTHALMOLOGY REPORT. E-l
APPENDIX F - PATHOLOGY REPORT F-l
APPENDIX G - PROTOCOL, AMENDMENTS, AND DEVIATIONS. G-l
paginated per source
\\f
-------
-------
'Study No. 5221.06
I. SUMMERY:
This study examined the toxic effects of ortho-cresol in Sprague
Dawley rats following 13 weeks of gavage administration. Dose levels studied
were 0, 50, 175 and 600 mg/kg/day. The biological effects of ortho-cresol
were generally restricted to the high dose level. ' Treatment-related central
nervous system depression was apparent for these animals and probably
contributed to their death. On only one occasion and at no other tine,
reversible CNS depression was also noted for two mid dose animals. No other
toxic manifestations were seen for ortho-cresol treated rats. Thus,
175 rag/kg/day for ortho-cresol administered to male and female Sprague Dawley
rats for 13 weeks appears to be the dose at or below which no significant-
toxicological effects other than transient weight and weight gain effects in
males and infrequent clinical signs of tremors and cona were observed.
II. INTRODUCTION;
This study was conducted to assess the toxicity of ortho-cresol
(o-cresol) in rats when administered for 13 weeks by gavage. Ml methods and
procedures were conducted in accordance with the appropriate Quality Assura-
nce Prograins (Microbiological Associates, Inc.; MBA or Pathology Associates,
Inc.? PAI) designed to conform with FDA Good Laboratory Practice Regulations.
III. MATERIALS AND METHODS:
A. Test Article
o-Cresol (99.5%), 4 kg, was received on 07/29/85 and was assigned
MBA chemical number 23. The source was Eastman Kodak Company,
Rochester, NY, 14650 (lot No. B12B). The test article was stored
in its original container at room temperature and ambient humi-
dity.
B. Animals
One-hundred and thirty Sprague Dawley rats of each sex were
obtained from Charles River Breeding laboratories, Inc., Lakeview
(Newfeld), NJ on September 4, 1985. The animals were approxi-
mately five weeks old upon arrival at MBA's animal facility. The
animals were in quarantine/pretest for 12 days prior to initiation
of treatment. Housing was by groups during quarantine and
individual during the treatment period. The animals were housed
on Beta-Chip hardwood bedding in polycarbonate cages which
accommodated aniinals up to the upper weight range reccramended in
the Guide_for the Care..and....Use of laboratory Animals, EHEW, (NTH)
No. 78.23. All test animals received Purina Laboratory Chow No.
-------
Study No. 5221.06
5001 in block form and water (Washington Suburban Sanitary
Commission, Potomac Plant) ad libitum.
During the study period, animals were housed in a temperature-
controlled room with a 12-hour light/dark illumination cycle.
Animal room temperature and humidity were recorded once daily and
were noted to be outside of the protocol-specified ranges on
several occasions during the study. Monthly environmental data
are summarized below:
Month/Year
9/85
10/85
11/85
12/85
Number of
Readjms
15
31
30
17
Mean
± S.D.
TEMPERATURE
76.8 ± 2.6
78.7 ± 3.3
78.1 ± 2.8
73.8 ± 3.6
Rancre
(degrees F
74-82
70-85
72-82
67-79
a
')
Number (%) of Readings
Within the Protocol-
Required Range
5 (33)
5 (16)
5 (17)
10 (59)
RELATIVE HUMIDITY f%)
b
9/85
10/85
11/85
12/85
15
31
30
17
Protocol-required
Protocol-required
52.
50.
35.
19.
range =
range =
2 ± 9
6 ± 11
8 ± 11
2 ± 10
69-75°
35-65%
.6
.9
.6
.2
F
39-65
30-80
12-58
8-42
15
27
16
2
(100)
(87)
(53)
(12)
C. Experimental Design
During the second week of quarantine, animals were examined by the
Staff Veterinarian and were found to be acceptable for use on
study. The animals were randomized on the basis of body weights
into four groups of 30 animals per sex. Ten male and ten female
rats were selected for baseline hematology and serum chemistry
determinations. Three additional rats/sex/dose were placed on
test for neuropathology studies. This phase of the study was
subsequently terminated in Test Week 2 following Sponsor request,
and the animals were discarded. The following dose levels were
selected by the Sponsor on the basis of preliminary studies which
included a two-week range-f inding/exploratory test (Appendix A),
and were administered once daily by gavage for at least 13
consecutive weeks.
-------
Study No. 5221.06
Treatment Dose Level Number of Animals Dosage Formulation
Group . (TO/kq/day) Male Female (mg/ml)
1 0 30 30 0
2 50 30 30 10
3 175 30 30 35
4 600 30 30 120
5 Baseline Clin. Path. 10 10
The test chemical was diluted in corn oil on a weekly basis to
achieve the above concentrations which allowed for a dosing volume
of. 5 ml/kg. The concentration of o-cresol in corn oil was
analyzed from dosage forms used during Test Weeks 1, 2, 4, 8 and
13 by ENSECO Inc., Cambridge, MA. Additionally, American Biogen-
ics Corporation, Decatur, IL tested the stability of o-cresol
dosage forms following a 14-day holding period. Finally, several
samples were subsequently sent to both ENSECO Inc. and American
Bicgenics Corporation for confirmatory analyses. Analytical
chemistry methodology can be found in Appendix B.
All rats on test received a unique test animal number which
appeared as an ear tag. A cage card appeared on the front of each
cage and contained the following information: study number,
animal number, test article name,•treatment group name or number,
room number, dose level, strain, sex, receipt date and start date,
The cage cards were color-coded as a function of treatmant group
and sex,
The test article or vehicle (corn oil) was orally administered
once daily for at least 13 consecutive weeks commencing on
16 September 1985. Animals were dosed up to the day prior to
routine necropsy in either Test Week 7 (interim kill) or 14
(terminal kill). The gavage procedure was accomplished by the use
of a rigid oral feeding needle.
Non-fasted body weights were recorded on Test Day 1 and weekly
thereafter. Individual food consumption data were collected on a
weekly basis. Moribundity/mortality checks were routinely
performed twice daily (once in the morning and once in the
afternoon), and moribund animals were killed and necropsied. The
test animals were examined once weekly for clinical signs of
toxicity.
Ophthalmology examinations were performed during the quarantine
period and in Test Week 13 by Dr. Nancy Brcmberg, Diplomate,
American College of Veterinary Ophthalmologists. This procedure
-------
Study No. 5221.06
was done by indirect cphthalnosoqpy, and only animals which were
free of visible lesions were considered for test aniitial selection.
Blood samples were collected from 10 rats per sex which were
designated for baseline clinical pathology determinations, 10 rats
per sex per dose sacrificed during Test Week 7, and 10 rats per
sex per dose sacrificed at study termination (Test Week 14},
Blood was obtained from the retro-orbial sinus following an
approximate 16-18 hour fasting period. The following hematology
and clinical chemistry tests were performed;
Hematploqy
Hemoglobin
Hematocrit
Erythrocyte count
Total and differential leukocyte count
Erothrombin time (FT)*
Activated partial thrombcplastin time (AFTT)*
Ifeticulocyte count
Clinical Chemistry
Sodium*
Qiloride*
Potassium*
Calcium*
C02
SGPI
SG0T
Glucose
BUN
Direct and total bilirubin
Alkaline Hiosphatase
Total cholesterol
Albumin
Globulin (calculated)
Total protein
A/G ratio (calculated)
Creatinine
Hiosphorus
* Test not performed at
baseline interval due
to technician error.
Urine specimens were obtained from 10 rats per sex per dose
sacrificed during Test Week 7 and from 10 rats per sex per dose
sacrificed at study termination. The urine specimens were
collected from metabolism pans into gauze-filtered urinalysis cups
-------
Study No. 5221.06
during the overnight fasting period. The following urinalysis
parameters were assessed:
Urinalysis
Appearance
Volume
Color
Specific gravity
PH
Protein
Glucose
Ketones
Bilirubin
Urobilinogen
Microscopic examination
Clinical pathology methodology is contained in Appendix C.
Complete gross necropsy examinations were performed on all rats
found dead during the study and those killed at the interim and
terminal sacrifices. Rats assigned to the interim sacrifice
(identified at study onset) were killed in random order over a
consecutive two-day period. At the terminal sacrifice, all
surviving rats were killed in random order over a consecutive
three-day period. All rats were anesthetized with 003 and
exsanguinated by bleeding from the posterior vena cava.
Animals were fasted overnight prior to necropsy. The necropsy
procedure included a thorough and systematic examination and
dissection of the animal viscera and carcass, and collection and
fixation of the following tissues/organs in 10% neutral buffered
formalin:
All gross lesions Corpus and cervix uteri
Brain (3 levels) ' Spleen
Eye ! Bone (with narrow)
Pituitary Skeletal inuscle
Salivary gland Lymph node (mandibular)
Heart Spinal cord
Thymus Mammary gland
Thyroid (with parathyroid) Aorta
Lungs (with mainstem bronchi) Sciatic nerve
Trachea . Liver
Esophagus Kidneys
Stomach Urinary bladder
Small and large intestine Testes
Adrenals Prostate
Pancreas Ovaries
-------
Study No. 5221.06
All of the above tissues for all control and high and mid dose
animals were submitted for histopathologic examination.
Histopathologic examination of the mid dose animals was performed
due to the high mortality rate in the high dose group.
During terminal sacrifice, in addition 'to terminal body weight,
the heart, liver, spleen, brain, kidneys (individually), gonads
(individually), adrenals and thyroid/parathyroid were weighed.
D. Statistical Analyses:
Body weight, food consumption, clinical chemistry, hematology and
organ weight data were analyzed by one-way, by sex, Analysis of
Variance tests with Dunnett's t test employed if a significant
F ratio was found (p < 0,05). Individual animal data can be found
in Appendix D.
IV. RESULTS;
A. Analyses and Stability of Dosage Form Preparations
o-Cresol in corn oil was found to be stable for at least 14 days
at the concentrations tested. Additionally, the analyses of the
dosage form preparations used during Test Weeks 1, 2, 4, 8 and 13
indicated that target concentrations were generally within an
acceptable range. At the 120 rag/ml target concentration, some of
the samples were assayed at levels up to 28% higher than expected.
When 16 additional samples were subsequently sent to both American
Biogenics Corporation and ENSECQ Inc. for confirmatory analyses,
significant witMn-sample/between laboratories variability was
observed. For example, sample C0658A85 with a target concentrat-
ion of 120 mg/ml assayed at 135.1 rag/ml, 12.6% over target, by
American Biogenics Corporation. ENSECO Inc., however, assayed
this sample at 118.5 mg/ml or 1.2% under target. In those few
cases where a sample was outside of 10% of the intended concentra-
tion, the assayed'value by the other laboratory was always within
range or outside of range but in the other direction (Tables
la-lc).
B. Mortality/Clinical Observations
Nineteen females and nine males at the 600 mg/kg/day dose level
died during the three month treatment period (Tables 2 and 3).
Postdosing observations revealed signs of central nervous system
(CNS) depression in male and female rats at the 600 mg/kg/day dose
level. Surviving and nonsurviving high dose animals became
-------
Study No. 5221.06
lethargic and experienced tremors within 15-30 minutes of dosing.
Biis phase was followed by a comatose state and convulsions in the
most severe cases. Dyspnea was also observed in high dose rats on
occasion.
Approximately one hour after dosing, the surviving animals
"recovered" and appeared normal. As shown below, the signs of CNS
depression were most frequently observed during the first four to
five weeks of the study and again during weeks 9 and 11:
Incidence of Significant Clinical Signs in High Dose Ratsa
OCMA.
M
M
M
1
2
3
4
5
9
10
11
13/30
19/28
10/26
9/24
12/24
11/13
1/12
8/12
30/30
24/28
16/24
10/18
14/18
3/6
-
5/6
9/30
9/28
4/26
— '
6/24
6/13
1/12
3/12
17/30
16/28
7/24
-
13/18
3/6
-
1/6
6/30
4/28
2/26
_
-
2/13
-
2/12
6/30
6/28
3/24
-
_
4/6
-
1/6
Number of animals exhibiting sign/number alive at
beginning of indicated week.
Only those weeks during which time relevant signs
were observed are presented.
High dose animals also became increasingly more difficult to dose
as the study progressed. The animals would contort their bodies
and attempt to resist the gavaging procedure.
One mid dose female demonstrated tremors and became comatose on
day 23 of the study, toother female from this group exhibited
lethargy and tremors on, day 27 of the study. These signs were not
seen at any other time for this dose group nor at the low dose
level. No other significant clinical signs were observed for
o-cresol-treated rats.
C, Body weight
Statistically significant (p < 0.05) reductions in body weight
were seen for males at the high dose level (600 mg/kg/day) during
weeks 2 through 10, and for those males receiving 175 mg/kg/day
during week 2 only. Body weights of females at those doses were
-------
Study No. 5221.06
unaffected by treatment. Only low dose females (50 mg/kg/day)
during weeks 6, and 8 through 14 showed significantly reduced body
weights, as cxanpared to controls.
Reductions in body weight gain were seen for males administered
175 and 600 mg/kg/day. The weight gains of the high dose males
were noted to be significantly lower than the controls durmg
weeks 1 through 9. A 30% reduction in weight gain was evident
following one week of treatment, however this reduction lessened
as a function of time and was only about 10% by study termination.
Sporadic significant weight gains were also observed for the
175 mg/kg/day dose group males for weeks l (decrease), and 10 and
11 (increases), as compared to the controls.
Body weight changes were not apparent for females at the high
dose. Low dose females showed a slightly greater rate of weight
gain than control animals which was noted to be statistically
significant at weeks 5, and 7 through 13. This was not seen for
mid or high dose females and was not considered biologically
significant. Body weight for low and mid dose males were
unaffected by o-cresol (Tables 4-7).
D, Food Consumption
Slight decreases In food intake were generally seen during the
first half of the study for males and to a lesser extent for
females at the high dose level. Significantly (p < 0.05) lower
than control mean food consumption values were noted for the high
dose males during weeks 1 through 6, and for the high dose females
during week 1. Sporadic increases and decreases were seen at the
other dose levels but were not considered biologically significant
(Tables 8 and 9).
S. Clinical Pathology
Clinical chemistry, hematology and urinalyses parameters did not
appear to be affected by o-cresol treatment. Sporadic increases
and decreases were seen which were not considered biologically
significant (Tables 10-17).
F. Ophthalmology
The Ophthalmology Report is contained in Appendix E. Treatment-r-
elated ophthalmic lesions were not seen for rats receiving
o-cresol.
-------
Study No. 5221.06
G. Organ Weights
Organ weights did not appear to be affected by o-eresol treatment.
Relative left and right kidney weights of the high dose sales were
noted to be slightly but not significantly elevated, as compared
to the control group values. The higher relative kidney weights
in this group appear to be a reflection of the slightly lower
terminal body weights of the high dose animals, other sporadic
increases and decreases in organ weights were seen which were not
considered biologically significant (Tables 18-21).
H. Pathology
The Pathology Report is shown in Appendix F, Treatment-related
gross and histomorphologic lesions were not in evidence. Although
28 deaths occurred among the high dose animals, the cause of death
was not determined from pathologic evaluations. lung lesions
including congestion and edema were in evidence for many of these
animals. They were, however, not considered a direct effect of
o-cresol and may have been associated with terminal stress. In
addition, oil droplets found in the lungs of these aniroals may
have been due to aspiration of o-cresol/corn oil during a convuls-
ive seizure. Additionally, none of the surviving high dose
animals demonstrated histatnorphologic changes of the lungs.
V. DISCUSSION;
This study evaluated the oral toxicity of ortho-eresol in Sprague
Dawley rats when administered for 13 weeks by gavage. Nineteen females and
nine males at the high dose died during the study. Clinically, surviving and
nonsurviving high dose anfooals showed QB depression and were generally
lethargic/ataxic with tremors and/or convulsions. These observations were
reversible for surviving animals as they generally appeared normal within one
hour after dosing. High dose males but not females also showed an approxim-
ate 10% reduction in body weight gained by the end of the 13-week treatment
period. With the exception of CMS depression observed for two mid dose
animals on one occasion, no other clinical effects of o-cresol were in
evidence.
Clinical chemistry, hematology, urinalyses, and organ weight measurem-
ents failed to detect treatment-related changes. In addition, ophthalmology
and pathology examinations did not identify o-cresol target organs. Thus,
the cause of death for high dose animals was not established. The central
nervous system appears clinically to be affected by o-cresol treatment.
In summary, the biological effects of o-cresol were generally restric-
ted to the high dose level under the conditions of the present study.
-------
Study No. 5221.06
Treatment-related central nervous system depression was apparent, and
probably contributed to the death of these animals.
VI. HSRSCMMgL!
L. T, Mulligan, Jti.D. served as Study Director, and was responsible
for the overall conduct of the study. Barry S. Levine, D.Sc., Diplomats,
American Board of Toxicology, was Study lexicologist and was responsible for
the in-life portion of the study and for clinical pathology evaluations.
Diana S. Copeland, DVM, Diplomats, American College of Veterinary Patholcgis-
ts, was responsible for gross necropsies and histopathologic evaluations.
John Miller, DVM, was responsible for laboratory animal care. Harry J.
Baulin, M.S., served as Study Chemist, and provided dosage formulations and
analytical chemistry services. Nona S. Karten, M.A., was responsible for the
Quality Assurance Program. Mite Schulz, B.S., and Brian Makle, B.S., were
responsible for the collection of in-life test animal data.
VII. ARCHIVES;
The raw data and final report are archived at Microbiological Associa-
tes Inc., 5221 River Road, Bethesda, MD 20816 with the following exceptions.
Pathology specimens including wet tissues, blocks and slides and original
necropsy forms are temporarily archived at Pathology Associates, Inc., 10075
Tyler Place, Hyatt Park II, Ijamsville, MD 21754 and will be transferred to
the MBA. Archives upon Sponsor approval of the final report.
10
-------
Study 5221,06
TABLE la
SUBCHRONIC TOXrCITY OF ORIHO-CPISOL IN SERAGUE DMCEY EMS
CDNCSNTRKTION OF ORIBD-CRESOL IN CORN OIL (ing/tal)
STABILITY ANALYSES3
Sample
Number
C0162A85
C0164A85
C0744A85
Date
Mixed
9/15/85
9/15/85
9/15/85
Target
Cone, (ma/ml)
10
120
120
Concentration (mar/ml)
Zero Day 14-Day
10,28b 10.15
127.3 • 123.4
126.2 117.3
Percent
Difference*
-1.3
-3.1
-7.1
*Percent Difference = 14-Day Value minus Zero DayJ/alue x 100
Zero Day Value
aAnalyses performed in duplicate by American Biogenics Corporation unless
noted otherwise.
^Analyses performed in triplicate.
-11
-------
Study 5221.06
to
TJiBLB li)
SUBCHRDNTG TOJOCTZY OF ORTHO-CRESOL IN SPRM3JE Dmi£¥
OF ORTHO-CRESOL IN OOKM OIL
Target
Concentration
(m/ml)
0
10
35
120
1
ND
9.1
37.8
141.5
FORMULATION AWALKSES3
2test Week
24 8 13
ND WD ND ND
5.5 10.5 9.8 10.5
39.2 40.2 37. 4 34.2.
143.3 153.1 128.6 136.8
aAnaIyses performed by EKSEQO Inc. (formerly EROO), Cambridge, MA unless otherwise noted.
ND - Not detected above the minimm reporting limit of 1.0 mg/ml.
-------
Study Wo. 5221.06
TABLE Ic
SOBCHSOMTC TOXICHY OF QFTHO-ORESOL IN SPRM3JE DWLEY
O3NFIRMMDI& MM.YSES OF OKTHO-CRESOL JN CORN OIL
Merican
Target Concentration Biogenics Corporation JEWSECO Inc.
Sample Mmter _ (ing/ml) _ Assay Values (mg/ml)a Assayed Values fmg/ml ) a
C0161M5 00 ND
C0502M5 0 0 ND
C05B7M5 0 0 ' ND
C0617A85 00 ND
C0185M5 35 38.0 30.3
C0256M5 35 37. 8 32.3 ,
C0834M5 35 38.9 30.4
C0974AB5 35 36. sP 30.0
C0164AB5 120 127.3 119.8 ,
CQ186A85 120 130.6 122.2
C0257M5 120 131.6 131.2
C0505M5 120 126. 6b 223.0
C0627A85 120 130.4 107.2
C0658A85 120 135.1 118.5
C0744A85 120 126.2 112.7
O0957A85 120 129.2 114.9
aMean of duplicate assays unless otherwise noted.
%ean of triplicate assays.
ND = Not detected above the minimm reporting limit of 0.1 ng/ml.
-------
Study No. 5221.06
TAHIE 2
suBCHRONie TOXICITY OF ORTHO-CRESOL
IN SPRAGUE DAWLEY RMS
Male Mortality Summary*
Test
Week
1
2
3
4
5
6
7
8b
9
10
11
12
13
14
0
mq/kq/day
30
30
30
30
30
30
30
20
20
20
20
20
20
20
50
mcr/kcr/dav
30
30
30
30
30
30
30
20
20
20
20
20
20
20
175
m/kq/dav
30
30
30
30
30
30
30
20
20
20
20
20
20
20
600
mq/ker/day
28
26
24
24
24
23
22
13
13
12
12
12
12
12
aSurvivors (n=30 through Test Week 1, and 20 thereafter).
b!0 rats/sex/dose were used for the scheduled interim kill during Test Week 7. Only 9 of the 10
initially identified interim-kill males at the 600 mg/Joy dose level were available.
-------
Study Ho. 5221.06
TABLE 3
SUBCHROHTC TOXfCmf OF ORTHO-CRESOL
IN SPRAGUE DAWLEY RATS
Female Mortality Summary
a
Test
Week
1
2
3
4
5
6
7
8b
9
10
11
12
13
14
0
msAkg/day
30
30
30
30
30
30
30
20
20
20
20
20
20
20
50
mg/kg/d BY
30
30
30
30
30
30
30
20
20
20
20
20
20
20
175
mg/kg/day
30
30
30
30
30
30
30
20
20
20
20
» 20
20
20
600
mg/kq/day
28
25
18
18
17
13
13
6
6
6
6
6
5
4
BSurvivors
-------
Study No. 5221.06
TABLE 4
SUBCHRONJC TOXICITY OF CSTHO-CSESOL IH SPRAGUE OAULEY RATS
HALE ICOY WEIGHT DATA (g)
TEST
WEEK 0 mg/kg/day 50 mg/kg/day 175 ing/kg/day 600 mg/kg/day
1 223 * 10C 30) 222 * 10( 30) 219 * 10( 30) 221 * SC 30)
2 2B2 ± 13( 30) 283 ± 15< 30) 270 t 16< 30)* 264 t 13C 28}*
3 324 t 17( 30) 328 ± 16C 30) 319 t Z2( 30) 304 t 16< 26)*
4 337 * 20< 30) 343 t . 19< 30) 333 t 29< 30) 313 t 17( 25}*
5 378 ± 23( 30) 384 t 22( 30) 377 t 26( 30> 348 t 21( 24)*
6 397 ± 24< 30) 406 * 24< 30) 397 t 39{ 30) 360 t 31( 24)*
7 430 t 27C 30) 439 ± 24( 30) 434 t 34( 30) 39! i 26< 23)*
8 450 * 28C 30) 451 ± 40< 30) 456 i 37C 30) 406 t 28< 23)*
9 476 t 33< 20) 483 t 33( 20) 475 t 38( 20) 436 ± 3S( 13)*
10 493 i 34< 20) 499 t 38( 20) 495 * 43< 20) 441 ± 49< 13)*
11 488 t 33{ 20) 498 t 42< 20) 518 ± 47< 20) 457 t 51( 12)
12 511 t 36C 20) 525 t 39C 20) 538 i 49C 20) 483 * 46{ 12)
13 530 * 37< 20) 542 t 43< 20) 552 t 52< 20) 498 * 45C 12)
14 547 ± 40( 20) 557 * 46( 20) 566 ± 52( 20) 514 ± 45C 12)
Weights taken on lest Day 1 prior to dosing.
* •- Statistically significant difference froai control group
using ANOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean ± standard deviation ( M )
16
-------
Study No. 5221.06
TABLE 5
SUBCHROHIC TQXICm OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
HALE BODY WEIGHT GA5H DATA (g)
TEST
UEE*C 0 tng/kg/day
1 59 t
2 102 ±
'3 114 t
4 155 *
5 174 i
6 207 *
7 227 *
8 253 t
9 270 1
10 266 t
11 2Sfl i
12 308 1
13 324 *
13(
17C
19C
23(
24 (
27<
27C
33(
34{
34<
38(
38(
41(
30}
30}
30}
30)
30}
30}
30}
20}
20}
20)
20)
20}
20)
50 mg/kg/day
60 i
106 *
121 t
162 ±
184 1
217 t
229 t
260 ±
277 *
276 t
303 ±
319 *
334 ±
IK
UK
14(
19C
20C
2K
37<
28(
34(
38{
35 (
40(
43(
30}
30)
30)
30)
30}
30}
30}
20)
20}
20)
20)
20}
20)
175 mg/kg/day
50 t
100 i
114 i
157 i
178 4
214 i
237 *
257 i
277 i
300 t
320 *
334 ±
348 J
8<
«C
21 C
20<
33 <
29C
32(
34C
40C
43(
46{
49<
49(
30)*
30)
30)
30)
30)
30)
30}
20}
20)
20)*
20}*
20}
20)
600 mg/kg/day
42 *
82 i
91 t
126 ±
137 t
168 t
183 ±
212 i
216 *
232 *
258 t
273 t
289 t
8( 28)
10( 26)
12( 25)
17( 24)
29( 24}
23 ( 23)
25 C 23)
31C 13)
47( 13}
49{ 12}
42( 12)
41( 12)
41 ( 12}
*
*
*
*
*
*
*
*
*
* -• Statistically significant difference from cantrsl group
using AMOVA and Dunnett's T-Test {P<=0.05).
Results presented as mean i standard deviation ( H )
17
-------
Study No. 5221.06
TABLE 6
SU8CHRQNIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE BODY y£lGHT DATA (g)
TEST
WEEK
1
2
3
4
5
6
7
8
9
10
11
12
13
14
0 mg/kg/day
155 ±
175 ±
198 i
201 t
220 *
222 ±
237 i
242 i
250 *
255 *
262 ±
267 t
269 t
' 274 t
8( 30)
10C 30)
12( 30)
12( 30)
14( 30)
14( 30)
15( 30)
15( 30)
15( 20)
16C 20)
14C 20)
1B( 20)
18( 20)
17( 20)
50
158
180
202
207
227
233
247
255
270
276
285
293
295
303
nig/kg/day
* 7( 30)
i 9( 30)
± 13( 30)
i . 13( 10)
± 15( 30)
± 17( 29)*
± 18C 30)
t 19( 30}*
t 22( 20)*
± 23C 20)*
± 25( 20)*
* 27C 20)*
± 30( 20)*
i 29{ 20)*
175
157 ±
179 i
201 ±
204 t
221 ±
229 t
241 4
245 t
257 ±
264 i
267 ±
276 ±
281 *
285 ±
ms/ki/day
9( 29)
13( 30)
15( 30)
16C 30)
2K 30)
19( 30)
20C 30)
22( 30)
21C 20)
24( 20)
24{ 20)
26 C 20)
25( 20)
24C 20)
600
154 ±
171 ±
192 *
196 t
215 t
220 ±
229 i
232 ±
239 t
248 i
256 *
262 t
270 t
273 t
ing/kg/day
IK 30)
12( 28)
14( 25)
14( 21)
18( 18)
16C 18)
15C 13)
17( 13)
23( 6)
20C 6)
19( 6)
20 ( 6)
21C 6)
19( 6)
Weights taken on Test Day 1 prior to dosing.
* -- Statistically significant difference from control group
using ANOVA and Ounnett's T-Tesr (P<=0.05).
Results presented as mean i standard deviation ( N )
18
-------
Study No, 5221.06
TABLE 7
SUBCHSOMIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE BOOT WEIGHT GAIN DATA (3)
TEST
WEEK 0 mg/kg/day
1 20 s
2 43 *
3 46 t
4 64 t
5 67 i
6 82 i
7 87 *
8 97 1
9 101 ±
10 108 ±
11 113 t
12 115 i
13 120 i
5{ 30)
8( 30)
9( 30)
9( 30)
11C 30)
12C 30)
12{ 30)
15C 20)
16( 20)
15C 20)
18( 20)
18( 20)
18( 20)
50 mg/kg/day
22 i
44 ±
49 t
69 t
75 *
89 1
97 i
112 i
118 t
127 ±
135 t
137 t
144 ±
5( 30)
7( 30)
9( 30)
11< 30)
12{ 29)*
14( 30)
15{ 30)*
17{ 20)*
18( 20)*
20( 20)*
22{ 20)*
25( 20)*
24( 205»
175 mg/kg/day
22 t
44 ±
48 1
65 1
73 i
85 t
89 t
101 t
108 t
112 ±
120 *
125 ±
129 t
6( 29)
8C 29)
9( 29)
15( 29)
12( 29)
14( 29)
17C 29)
16( 19)
19C 19)
18( 19)
21( 19)
21 ( 193
21C 19)
6DO mg/kg/day
18 i
39 *
42 ±
60 ±
65 i
74 t
77 *
81 t
91 t
98 i
105 t
113 i
116 t
5C 28)
7< 25)
7( 21)
1.1 C 18)
11C 18)
12{ 13)
12{ 13)
21< 6)
18C 63
18( 6)
20( 6)
21 C 6)
20C 6)
Statistically significant difference from control group
usins ANOVA and Ounnett's T-Test (P<=0.05).
Results presented as mean i standard deviation ( N )
19
-------
Study Ho. 5221.06
TEST
TABLE 8
SU8CHRONIC TOXICITY OF DRTHQ-CRESOL IN SPRAGUE DAULEY RATS
HALE FOOD CONSUMPTION DATA Cg/day)
WEES
1
2
3
4
5
6
7
8
9
10
11
12
13
0 mg/ki/day
23.7 ±
25. S 4
25.1 *
25.1 i
25. D t
25.8 *
22.4 i
22.0 t
15.8 i
21.71
23.5 4
23.2 1
22.1 i
2.0(
4.2C
3.6C
2.9(
2.5C
3.3C
5. 1C
3. 1C
3.7(
4.K
2.6<
2.6(
2.9C
30)
30)
30)
30}
30)
30)
30)
20)
20)
20)
20)
20)
20)
50 mg/kg/day
23. 5 t
27.2 ±
24.7 i
24,7 4
24.6 ±
23.7±
19.4 i
20.8 4
15.6 i
21.7 ±
23.0 i
21.2 4
20.8 t
1.6(
2.10
2.9(
2.4<
2.2(
3.5C
6.6(
3.2(
4.7(
2. 1C
2.3(
3.7<
4.4<
30)
30)
30)
30)
30)
30)*
30)*
20)
19)
20)
20)
20)
20)
175 mg/ki/day
22.6 t
25.7 *
23.4 4
26.3 *
24.7 i
25.7 i
23.4 *
22.3 4
24.4 *
22.9 ±
23.6 t
23.0 i
22.0 ±
2.9(
3. 1C
2.6<
2.6<
3.K
2.9{
3.9(
3.7(
4.0C
3.3<
3.2(
3.3C
4.2C
30)
30)
30)
30)
30)
30)
30)
20)
20)*
20)
20)
20)
20)
600 mg/kg/day
21.1 *
22.3 t
21.7 i
23.3 ±
22.9 s
22.1 4
19.8 ±
19.5 t
20.8 t
21.2 4'
23.3 4
23.7 i
22.3 4
2.7< 28)'
4.3C 27}<
2.4{ 24)'
2.6( 24}'
2.4C 24)'
2.5C 23)'
2.6C 23)
5.2( 13)
5.2( 13)*
6.K 13)
3.4{ 12)
3.2( 12)
3.7C 12)
* •- Statistically significant difference from control group
using ANOVA and Dunnett's T-Test
-------
Study No. 5221,06
TAiLE 9
SUBCHRONIC TOXIC1TY Of QRTHQ-CRESOl IN SPRAGUE DAWLEY RATS
FEMALE FOCC CONSUMPTION DATA (g/day)
TEST
WEEK
1
2
3
4
5
6
7 •
8
9
10
11
12
13
0 mg/kg/day
15.5 *
17.1 *
18.1 t
16.7 t
16.5 t
16.9 *_
13.9 i
14.1 ±
14.3 ±
14.8 t
14.1 t
13.7 *
13.8 ±
1.6
6.9
6.3
2.7
3.0
3.5
2.3
1.7
2.5
3.3
2.5
1.3
1.9
(30)
(3D)
(30)
(30)
(30)
C30)
(30)
(20)
(20)
(20)
(20)
(20)
(20)
50 ms/kg/day
14.5 ±
17.0 t
16.3 t
16.5 t
16.3 i
16.3 ±
14.8 i
14.3 t
15.8 i
15. 7 i
15.1 i
14.5 i
15.3 t
3.0
3,6
2.4
3.1
3.1
2.0
6.0(
3.2
2.0
1.8
2.0
1.8
1.8
(30)
(30)
(30>
(30)
(30)
(30)
29)
(20)
(20)
(20)
(20)
(20)
(20)*
175 mg/kg/day
16.0 i
15.5 4
16.0 ±
16.2 t
16.0 i
15.8 t
13.8 ±
14.1 ±
14.3 ±
14.5 t
14.2 ±
13.8 t
14.0 t
1.8
3.8
6.0
3.6
2.7
2.3
2.5C
1.6
3.9
3.7
2.8
2.1
1.5
(30)
(30)
(30)
(30)
(30)
(30)
29)
(20)
(20)
(20)
(20)
(20)
(20)
600 mg/kg/day
13.7 ±
14.2 t
14.7 t
15.7 *
15.1 i
16.3 t
1V. 9 t
14.0 i
14.2 t
14.5 ±
14.6 ±
14.5 ±
13.1 t
1.9 (28)*
3.6 (28)
4.8 (18)
2.6 (18)
2.2 (17)
5.2 (13)
2.1 (13)
2.6 (6)
1.6 (6)
1.9 (6)
1.8 (6)
1.4 (6)
2.0 (6)
Statistically significant difference from control group
using ANOVA and Dunnett's T-Test (P<=0,05).
Results presented as mean 4 standard deviation ( H )
21
-------
Study No. 5221.06
Parameter
TABLE 10
SUBCHROHIC TQXICITY OF ORTHO-CRESOl 1H SPRAGUE DAWLEf RATS
MALE HEMATOLOGr VALUES •
[Interim Sacrifice]
0 mg/kg/day 50 mg/kg/day 175 mg/kg/day 600 mg/kg/day
7.87 * 0.36< 10} 8.10 i 0.56C 10) 7.94 ± 0.29C 10) 7.75 ± 0.51C 9)
15.6 1 0.5C 10} 15.7 i 0.9C 10} 15.4 t 0.5C 10} 15.3 ± 0.5< 9)
43.5 ± 2.2< 10) 44.2 i 2.9< 10) 44.4 t 1.5C 105 43.8 ± 2.0C 9)
RBC
(x 10'
HCB
(g/dl)
HCT
PT 11.8 * 0.6C 10) 11.7 i 1.1C 10) 11.9 * '0.8C 9) 11.4 * 0.6C 9)
(sec.)
APTT 30.7 * 2.0C 10) 33.9 i 3.2C 10) 32.9 i 2.5C 9) 32.6 t 2.3C 9)
(sec.)
RETIC 0.9 ± 0.3( 10) 0.7 ± 0.4( 10) 0.8 ± 0.5( 10) O.B i 0.6C 9)
(% rbc)
Results presented as mean ± standard deviation < N )
22
-------
Study Mo. 5221.06
TABLE 10 (continued)
SUBCHROM1C TOXIC1TY OF QRTHO-CRESOL IK SPRACUE DAULEY RATS
MALE HEMATQLOGY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day 50 tng/kg/day 175 ing/kg/day 600 mg/kg/day
WC 16.7 ± 3.2( 103
Cx IQ'
14.6 t 3.6( 10) 14.2 ± 2.71 10} 14.8 ± 2.3( 9}
SEGS 1.4 t 0.8(103 1 .4 i 1.0(10) 1.6* 0.8(10) 1.8 1 0.8( 9}
0.1 i 0.2( 10) 0.0 t 0,0( 10} 0.0 * O.U 9)
12.6 ± 3.0( 10) 12.0 * "2.5C 10) 12.5 4 2.4< 9)
(x
BANDS 0.0 4 O.K 10)
(x 1QA3/m*3)
LYMPHS 15.0 1 2.9( 10)
(x 10*3/mmT3)
(x
MONO 0.2 i 0.2C 10) 0.3 t 0.2( 10) 0.3 4 0.3< 10) 0.3 * 0.3C 9)
0.1 4 0.1( 10) 0.2 4 0.3( 10> 0.1 * 0.2( 10) 0.1 i 0.2C 9)
EOS
Results presented as mem t standard deviation ( N )
23
-------
Study No. 5ZZ1.0A
TABLE 11
SUBCHSONIC TCXICITY OF ORTHO-CRESQL 1H SPRAGUE DAWLEY RATS
MALE HEMATOLOGY VALUES
[Terminal Sacrifice]
Parameter 0 mg/kg/day 50 mg/kg/day 175 Mg/kg/day 600 mg/kg/day
RBC 8.62 ± 0.27( 10) 8.55 i 0.41( 10) 8.57 ±.0.47( 10) B.5B i 0.61C 6>
IK 10*6/mm"3)
HGB 15.2 * 0.4( 10) 15.2 ± 0.4( 10) 15.4 t 0.5C 10) 15.4 i 0.5< 6)
Cg/dl)
HCT 43.3± 1.4( 10) 42.9* 1 .9( 10) 44,1 s 1.7C 10) 43.91 1.8C 65
PT 10.7 t 2.1< 10) 11.1 t 1.6C 10) 12.2 ± "0.7< 10) 10.71 3.5( 6)
(sec.)
APTT 34.4 ± 4.6( 10) 33.8 ± 2.5C 10) 32.9 i 5,6( 10) 30.1 t 9.8( 6)
(sec.)
RiTIC 0,91 0.4(10) 1.1 ±" 0.9(10) 1.5 ± 0.9(10) 1.3 ± 1.4( 6)
(% rbc)
Results presented as mean t standard deviation < N )
24
-------
Study No. 5221,06
TABLE 11 (continued)
SUBCHROHIC TCX1CITY OF CRTHO-CRESOL IN SPRAGUE DAWLEY RATS
HALE HEHATOIOGY VALUES
[Terminal Sacrifice]
Parameter 0 rog/lcg/day 50 mg/kg/day 175 mg/kg/day 600 mg/kg/day
UBC H.3 ± 2.1C 10) 12.6 * 2.6C 10} 14.0 * 2.3< 103 14.2 ± 3.4( 6)
(x 10"3/imr3>
SEGS 2.8 i -2.0C 10} 2.2 ± 1.2C 10) 2.5 t 0.9< 10) 2.1 i 1.4( 6)
(x 10*3/rmr"3)
BANDS 0.1 i O.H 10) 0.1 i O.K 10) 0.0 ± 0.1( 10) 0.1 * 0.1( 6)
(x 10A3/rra*3)
LYMPHS 11.1 i 1.7( 103 9.7 t 2.2( 10) 11.0* 2.5( 10) 11.4 t 3.5< 6)
(x 1tr3/nnT3)
HWO 0.2 * 0.2< 10) 0.5 i 0.4( 10) 0.3 ± 0.2( 10) 0.5 i 0.4< 65
(x 10*3/11111*3}
IDS 0.1 ± O.K 10) 0.0 i O.K 10) 0.1 i 0.1C 10) 0.1 ± 0.1< 6)
(x lO'S
Results presented as mean * standard deviation ( N )
25
-------
Study No. 5221.06
TABLE 12
SUBCHRONIC TOXICITY OF QRTHO-CRESOL IM SPRAGUE BAWLS? SATS
FEMALE HEHATOLOGT VALUES,
Unterim Sacrifice]
Parameter 0 mg/kg/etey 50 mg/kg/day 175 mg/kg/day 600 mg/kg/day
\
RIC 7,98 i 0.20C 10) 7.89 * 0.36< 9) 7.55 ± 0.47t 10) 7.71 ± 0.33( fi)
(x 10*6/11111*3)
HG8 15.6 i 0.4C 10) 15.7 * 0.8C 9) 15.3 * 0,6( 10) 15.3 * 0.3( 6)
(S/dl)
HCT 44". 2 ± 1.3(10) 43.6 ± 2.41 9) 41.6 t 2.6( 10) 43.1s 1.3( 6)
PT 11.0 ± 0.5C 10) 10.7 4 0.6C 10) 10.9 ± -1.1( 10) 11.6 ± 1.1C 6)
(sec.)
APTT 35.3 t 5.8C 10) 33.9 i 4.0C 10) 34.0 S 4.9< 10) 36.4 t 4.3( 6)
Csec.)
R6T1C 0.8 t 0.7< 10) 0.7 i O.SC 10) 0.6 ± 0.4< 1C) 1.9 ± 1.3{ 6)*
<.% rbc)
* -- Statistically significint difference from control group
using AKOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean t standard deviation ( N )
26
-------
Study No. 5221.06
Table 12 (continued)
SUBCHROMIC TOXtCITY OF QRTHQ-CRESQl IN SPRAGUE DAULEY RATS
FEMALE HEMATOLOGY VALUES
[Interim Saerifice]
Parameter 0 mg/kg/day 50 mg/kg/day 175 mg/ki/day 600 mg/kg/day
USC 10.9* 2.4(10} 12.7 t 4.7(9} 12. It 1.9<10} 13.7* 3.6 {63
(X 10A3/mm"3}
SEGS 1.0 t 0.4 (105 1.5 i 1.4 (9) 1.4 i D.9 (10) 1.8 ± 1.1 £6}
BANDS 0.0 i 0.1 (105 0.0 i 0.0 <9) 0.0 ± 0.1 (10) 0.0 t 0.0 (65
(x 1
LYMPHS 9.5 t 2.1(10) 10.9* 4.0(9) 10.4 i 1.6(10} 11.71 3.7(6)
Cx 10*3/nm*3)
MONO 0.2 ± 0.1 (10) 0.3 t 0.3 (9) 0.2 i 0,2 CIO) 0.2 ± 0.2 (6)
(x KTS/flm^)
EOS 0.1 ± 0.1 (10) 0.1 t 0.1 (9) 0.1 i 0.1 (10) 0.0 i 0.1 (6)
(x 1
Results presented as mean ± standard deviation ( K J
27 _
-------
Study Ho. 5221.06
Parameter
RSC
TABLE 13
SUBCHRQNIC TOXICITY OF ORTHQ-CRESQL IN SPRAGUE DftULEY RATS
FEMALE HEHATOLOGy VALUES
ITerainal Sacrifice]
0 mg/kg/day 50 mg/kg/day 175 mg/kg/day 600 mg/kg/day
8.43 ± 0.43 (10) 8.36 ± 0.27 (10) 8.31 t 0.43 (103 8.38 t 0.59 (4)
15.8 * 0.7 (10) 15,8 t 0.5 (10) 15.4 ± 0.7 (10) 15.6 ± 0.5 (4)
44.0 * 2.5 (105 44.2 i 1.3 (10) 43.3 i 2.0 (10) 44.6 t 1.8 (4)
(x
HGB
(9/dl)
HCT
PT 10.9 * 0.7 (10) 11.0 ± 1.2 (10) 10.6 ± -2.0 (10> 10.7 t 0.4 (4)
(sec.)
APTT
(sec.)
32.9 i 6.1 (10) 33.2 1 3.4 <10) 36.1 1 7.8 (10) 36.4 * 9.0 <4)
RET1C 1.2 * 0.8 (10) 0.8 1 0.4 (10) 1.3 * 0.7 (10) 1.4 i 0.4 (4)
(X rbc)
Results presented as mean i standard deviation ( N )
28
-------
Study Mo, 5221.06
TABLE 13 (continued)
SUBCHRQNIC TCXIC1TY OF ORTHO-CSESOL IN SPRAGUE DAWLEY RATS
FEMALE KEMATCLQGY VALUES
[Terminal Sacrifice]
Parameter 0 mg/kg/day 50 ing/kg/day 175 mg/k§/day 600 mi/kg/day
UBC 10.5 t 2.3( 10) 9.6 i 2.4( 10) 8.9 i 1.5( 10) 10.9 i 0.8(- 4)
(x 10"3/mm*3)
SEGS
(x
BANDS
1.9 * 1.5C 10) 1.4 t 0.5( 10) 1.4 i O.S( 10) 2.2 i 1.7( 4)
0.1 ± O.K 10) 0.1 ± O.K 10) 0.0 i O.K 10) 0.0 t O.OC 4)
LYMPHS
8.1 t 1.9( 10) 7.9 t 2.0( 10) 7.1 t* 1.S( 10) 8.7 t 1.9( 4)
(x
HONO 0.3 ± 0.2( 10) 0.2 t 0.2( 10} 0.2 ± O.K 10) 0.0 * O.K 4)*
* •• Statistically significant difference from control group
using ANOVA and Dunnett'S T-Test (P«0.05).
Results presented as mean ± standard deviation ( H >
29
-------
Study Ho. 5221.06
TABLE 14
SUBCHRONIC TOXICITY OF ORTHO-CiESOL IN SPRAGUE UAULEY RATS
MALi CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day 50 mg/kg/day 175 nig/kg/day 600 mg/kg/day
GLU 170.4 * 35. 4< 10) 182.9 t 47. 2C 10) 215.8 ± 48. 9< 10) 209.9 I 70. 2C 9}
SCOT 77 * 9( 10) 72 t 9< 10) 73 ± 5( 10) 79 t 11( 9)
T PRO 6.7 1 0.51 10) 6.5 1 Q.3( 10) 6.6 ± 0.4C 10) 6.5 s Q.4< 9)
(S/dl)
ALi 3.8 ± 0.2< 10) 3.7 ± 0.2( 10) 3.8 1 0.2C 105 3.8 ± 0.1( 9)
Ca/dl)
GLOB 2.8 ± 0.4( 103 2.8 * 0.2C 103 2.8 t 0.2< 10> 2.7 i 0.3{ 9)
(9/dl)
ALB/GLOB 1.364 * 0.162C 105 1.314 * 0.126C 10) 1.355 t 0.114( 10) 1.419 * 0.124C 93
(ratio5
CHOL 70.0* 13.7(10) 65.3 t 11.0(10) 58.9 ± 14.3(10) 70.9* 13. 4( 9)
(mg/dl)
* •• Statistically significant difference from control group
using ANOVA and Dunnett's T-Test
-------
Study No. 5221.06
TABLE 14 (CONTINUED)
SUBCHRONIC TQXJCITY OF ORTHO-CRESOL IN SPRABJE OAWIIY RATS
MALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day 50 mg/ks/diy 175 mg/kg/day 600 mg/kg/day
D BIL 0.02 i 0.01 (10) 0.02 * 0.01 (10) 0.02 ± 0.01 C10) 0.02 * 0.01 (9)
(mg/dl)
T BIL 0.15 t 0.04 (10) 0.16 1 0.04 (10) 0.14 t 0.05 (103 0.16 ± 0.04 (9)
(mg/dl)
CA 12.4 ± 1.4 (10) 12.6 * 1.5 (10) 13.1 i 1.6 (10) 12.4 ± 1.1 (9)
(mg/dl)
Na 145 t 5 (10) 145 t 6 (10) 152 ± 14 (10) 146 t 7 (9)
(Meq/l)
K 7.9± 1.4(10) 7.7 i 1.7(10) 7.2* 1.5(10) 7.9* 2.2(9)
(Meq/l)
CL 101 t 4 (10) 101 ± 5 (10) 102 i 8 (10) 102 t 7 (9)
(Meq/l)
AU PHOS 141 ± 53 (10) 127 t 81 (10) 152 i 81 (10) 124 t 77 (9)
C02 26 ± 3 (10) 24 ± 3.4 (10) 25 t 4 (10) 24 i 5 (9)
(Meq/l)
CREAT 0.71 ± 0.07 (10) . 0.74 t 0.09 (10) 0.70 t 0.07 (10) 0.71 i 0.07 (9)
(mg/dl)
.PHOS 10. B i 0.6(10) 10.0* 1.1(10) 10.6 t 0.9(10) 10.7* 1.3(9)
(mg/dl)
Results presented as mean t standard deviation ( N )
31
-------
Study No. 5221.06
TABLE 15
SUBCHRON1C TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
MALE CLrSICAL CHEMISTRY VALUES
[Terminal Sacrifice]
Parameter 0 mg/hg/day 50 mg/kg/day 175 mg/kg/day 600 mg/kg/day
CLU 236.8 ± 58. 1< 10) 226.2 i 59. 9< 10) 248.3 i 33. 2( 10) 187.5 ± '43. U 10}
(mg/dl)
BUN 14.3 i 2. K 10) 12.fi ± 2.6< 10) 13.8 t 2.0C 10} 14.1 * 2.6C 10)
Cmg/dl)
SGPT 80 ± 144( 10) 35 t 2?< 10) 39 i 22( 10) 88 ± 179C 10)
(lu/l)
SCOT 130 i 161( 10) 85 t 56< 10) 85 1 24( 10) 137 ± 2Q4< 10)
T PRO • 6.7 t 0.7< 10) 6.Z t 1.0C 10) 6,7 * 0.4( 10) 6.3 ± 0.7C 10)
(i/dl)
ALS 3.7 t 0.3( 10) 3.3 ± 0.3( 10) 3.7 i 0.2( 10) 3.6 ± 0.3C 10)
GLQB 3.0 ± 0.4( 10) 2.4 t 0.9C 10) 3.0 t 0.3C 10) 2.7 i 0.5( 10)
Cg/dl)
ALB/GLOi 1.258 t 0.095< 10) 1.818 t 0,819( 10)* 1.248 J 0.125( 10) 1.351 ± 0.231C 10)
(ratio)
CHOL 82.7 ± 24. 1< 10) 70.8 i 17.0( 10) 69.2 ± 12. 3( 10) 83.0 ± 27.3C 1C)
(mg/dl)
-- Statistically significant differtnce from control group
using ANOVA and Ounnett's T-Test
-------
Study Mo. 5221.06
TABLE 15 (continued)
SUBCHRONIC TOXICITY OF QRTHQ-CRESOl IN SPRA2UE DAUIEY RATS
HALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
Pen-meter 0 ms/kg/day 50 mg/kg/day 175 mg/kg/diy 600 rng/kg/day
0 B1L 0.02 i O.OH 10) • 0.01 i Q.OU 103* 0.01 ± O.Q1( 10) O.DE ± 0.01( 10)
(mg/dl)
T Bll 0,10 ± O.Q4( 10) O.Q8 i Q.03( 10) 0.09 i 0.04( 10) 0.11 i 0.07( 10)
(mg/dl3
Ca 12.1 * 1.K 10) 12.6 t 0.9( 10) 12.4 t 1.3< 10) 11.7 i 1.1( 10)
(mg/dl)
Na 152 * 7C 10) 151 t 6< 103 153 ± 5( 10) 155 t 7C 93
(Heq/l)
K 9.1 t 2.3(103 7.4 i 1.4(10) 8.2* 1.7(10) 7.5 i 1.3( 9)
(Heq/l)
Cl 100 i 6( 103 99 t 6( 10) 101 1 4( 10) 99 t 5( 9)
(Heq/l)
ALK PHOS 95 t 49( 10) 74 * 33( 10) 78 t 35( 10) 70 t 32( 10)
Uu/l)
C02 21 ± 4( 10) 21 * 2( 10) 23 t 3( 10) 22 s 3< 93
(Heq/l)
CREAT 0.75 1 0.06( 10) 0.72 t Q,1Q< 10) 0.71 ± 0.08C 10) 0.71 t 0.08( 10)
(mg/dl)
PHOS 10.0 t 1.3( 10) 8.2 * 1.1( 10)* 9.9 t 1.9( 10) 9.3 1 1.2C 10)
(mg/dl)
* •- Statistically significant difference from control group
using ANOVA and Dunnett's T-Test CP<=0.05).
Results presented as mean 1 standard deviation ( N 3
33
-------
Study No. 5221.06
TABLE 16
SUBCHRONIC TOXICITY OF CRTHO-CRESOL IN SPRACUE OAKLEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day SO mg/kg/day 175 mg/lcg/day 600 mg/kg/day
GLU 160.9 t 43. OC 10) 194.2 ± 69. 9< 10) 179.2 ± 41. 3< 10) 215. S * 69. 21 7)
(mg/dt)
BUN 14.9 ± 3.0C 10) 16.7 ± 2.3< 10) 16.9 * 4.1( 10) 14.9 ± 2.3C 7)
(mg/dt)
SCPT 35 ± 7( 10) 34 * 10( 10) 40 * 11( 10) 46 t 13C 7)
CIu/l)
SGOT 74 ± 4( 10) 71 t 14( 10) 81 i 11( 10) 78 ± 9( 7)
T PSO 6.8 * 0.4C 10) 6.8 ± 0.6( 10) 6.9 ± 0.7C 10) 6.9 t 0.6C 7)
(g/dl)
ALB 4.1 t 0.2C 10) 4.1 ± 0.3( 10) 4.1 t 0.3C 10) 4.0 ± 0.7C 7)
(g/dl)
GL08 2.7 ± 0.3( 10) 2.7 t 0.4( 10) 2.7 ± 0.4( 10) 2.7 t 0.3C 7)
ALB/GLOB 1.534 ± 0.183( 10) 1.564 ± 0.193< 10) 1.533 t 0.170( 10) 1.499 t Q.264C 7)
Cratio)
CHDL 80.3 ± 12.9( 10) 75.5 t 27.f( 10) 81.7 ± 11. 1( 10) 85.9 ± 14. 2C 7)
(mg/dl)
Results presented as mean * standard deviation ( N )
34
-------
Study No. 5221.06
TABLE 16 (continued)
SU8CHSOK1C TOXICITY OF ORTHO-CSESOL IN SPRAGUE DAULEY RATS
FEHALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
Parameter 0 mg/kg/day 50 rng/kg/day 175 mg/kg/day 600 mg/kg/day
D Ell 0.01 t 0.01 (10) 0.02 t 0.02 (10) 0.02 ± 0.02 £10) 0.01 i 0.01 (7)
(mg/dl)
T BIL 0.14 * 0.05 (10) 0.15 i 0.04 (10) 0.15 t 0.04 (10) 0.18 * 0.04 (7)
(mg/dl)
Ca 14.0 ± 1.1 (10) 12.8 ± 1.7 (10) 13.1 i 1.1 (10) 13.4 ± 1,3 (7)
(mg/dl)
Na 147 i 8 (10) 153 ± 14 (10) 156 ± 20 (10) 144 i 3 (7)
(Heq/l)
K 8.9 i 2.0 (10) 8.4 t 1.1(10) 8.6 i 1.1(10) 8.5 ± 1.2(7)
(Heq/l)
Cl 104 ± 8 (10) 108 t 14 (10) 112 i 19 (10) 101 * 4 (7)
CKeq/l)
ALK PHOS 93 t 29 (10) 111 ± 94 (10) 104 * 52 (10) 94 t 32 (7)
CIu/l)
C02 - 22 s 3 (10) 23 ± 3 (10) 21 i 4 (10) 20 i. 4 (7)
(Meq/l)
CSEAT 0.67 i 0.06 (10) 0.69 * 0.07 (10) 0.72 t 0.09 (10) 0.75 i 0.09 (7)
(mg/dl)
PHOS 10.21 0.9(10) 9.64 1.2(10) 10.0 ± 0.8(10) 9.6 ± 0.6(7)
(ingM)
Results presented as mean i standard deviation ( M )
35
-------
Study No. 5221.06
T/.BLE 17
SUBCHRON1C TOX1CITY OF CRTHO-CRESOL IH SPRAGUE DAULEY RATS
FiHALi CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
Parameter 0 rag/kg/day 50 mg/kg/day 175 mg/kg/day 600 mg/kg/day
GLU 177.0 t 47. 6C 103 1B5.3 ± 45. 7< 10) 193.5 1 43. 9( 10) 150.1 t 18. 7( 4)
BUM 14.6 t 1.4C 10) 13.2 * 3.2( 10) 15.7 ± 3.2C 103 16.4 t 2.7C 43
(mg/dl)
SGPT 24 * 4( 10) 32 t 17C 10) 40 t 23{ 10) 30 ± 11( 4)
Clu/l)
SCOT 75 * 15( 10) 86 ± 26( 10) 93 t 40{ 10) 83 ± 29C 4)
CIu/l)
T PRO 6.7 ± 0.9{ 10) 6.8 t 0,9< 10) 7.4 * 0.7( 10) 6.8 ± 0.7C 4)
(i/dl)
ALB 4.2 1 0.4{ 10) 4.4 1 0.3( 10) 4.4 t 0.4( 10) 4.1 ± 0.4C 4)
-------
Study Ho. 5221.06
TABLE 17 (continued)
SU8CHRONIC TOXICITT OF ORTHO-CRESOL JN SPRAGUE DAWLEY BATS
FEMALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
Parameter 0 mg/kg/day 50 mg/kg/day 175 mg/kg/day 600 mg/kg/day
0 B1L 0.01 ± O.OK 10} 0.01 t O.OK 10} 0.02 ± 0.01C 10} 0.01 ± O.OH 4)
(mg/dl)
T BIL 0.09 t 0.04( 10} 0.09 t O.Q3£ 10) 0.09 i 0.06< 10} 0.09 i 0.04C 4}
(mg/dl)
CA 13.0 ± 1.0( 10} 13.2 i 0.9C 10} 13.2 t 1.5( 10) 12.4 i 1.2( 4)
-------
Study Ho, 5221.06
TABLE 18
SUBCHROM1C TOXICITY OF ORTHO-CRESOL IN SPRAGUf DAWLEY RATS
RELATIVE HALE ORGAN WEIGHT DATA « Terminal Body Weight)
[Terminal Sacrifice]
Organ
HEA8T
LIVES
SPLEEN
KIDNEY-LFT
KIDNEY-RT
TESTIS-LFT
TESTIS-RT
ADRENALS
BRAIN •
THr./PARA.
0 mg/kg/day
0.318 t
3.337 ±
0.142 *
0.365 ±
0.370 *
0.312 ±
0.317 *
0.010 i
0.40S *
0.006 ±
0.02K
Q.246C
o.om
0.036C
0.034C
Q.Q39C
0.029C
0.002(
0.027C
0.002C
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
50
0.332
3.450
0.150
0.386
0.395
0,318
0.325
0,011
0.423
0.006
mg/kg/day
± 0.09U
1 0.911s;
4 0.042C
* 0.11K
± 0.118C
* 0.120C
i 0.123C
* 0.004C
* 0.09BC
± 0.003(
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
175 rag/kg/day
0.315
3.315
0.133
0.384
0.382
0.319
0.319
0.010
0.404
0.006
t 0.027C
i 0.271C
± 0.014{
± 0.038C
1 0.037C
i 0.032C
± 0.032C
I 0.002C
i 0.037(
± O.OOK
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
600 mg/kg/day
0.324 t Q
3.524 i 0
0.139 i 0
.019( 12)
.318( 12)
.012( 12)
0.423 ± 0,037< 12)
0.429 t 0
0.340 * 0
0.337 i 0
0.011 s 0
0.432 t 0
0.006 t 0
.039C 12)
.033C 12)
.035C 12)
.001 ( 12)
.031 ( 12)
.001 ( 12)
Results presented as mean i standard deviation ( N )
38
-------
Study No. 5221.06
TASLi 19
SUBCHSONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA C% Terminal Body Weight}
CTerminal Sacrifice]
Organ
HEART
LIVER
SPLEEN
KIDNEY-LFT
KIDKEY-RT
OVARY -LFT
OVARY -ST
ADRENALS
BRAIN
THY.
0 mg,
0.354 *
3.205 1
0.191 ±
0.384 t
0.396 *
0.016 *
0.016 i
0.024 t
0.762 S
0.009 ±
^kg/day 50 mg/kg/day ,
0.038<
0.240(
0.017<
0.045<
0.053<
0.006(
0.005<
Q.004C
Q.042C
0.003C
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
0.367
3.148
0.178
0.382
0.394
0.014
0.015
0.022
0.673
0.008
* Q.04SC
i 0.199C
i 0.019C
± Q.030C
± 0.037C
t 0,005(
* 0.004<
± 0.005(
± 0.10U
t 0.002C
20)
20)
20)
20)
20)
19)
18)
20)
19)*
20)
175 mg/lcg/day
0.357 t
3.218 i
0.194 ±
0.390 t
0.413 t
0.016 ±
0.017 t
0.023 *
0.720 t
0.009 i
Q.Q37C
0.255C
0.024C
0.049C
0.068C
0.005C
0.004C
0.005C
0.132C
0.003(
203
203
203
205
20)
20)
20)
20)
19)
20)
600 mg/kg/day
0.359 ± 0
3.319 t 0
0.204 i 0
0.388 i 0
0.400 t 0
0.019 t 0
0.014 t 0
0.027 t 0
0.800 t 0
0.011 t 0
.037( 4)
.177C 4)
.038C 4)
.023( 4)
.016C 4)
.C05C 4)
.005C 4)
.002( 4)
-034C 4)
,002( 4)
* •• Statistically significant difference from control group
using ANOVA and Dunnett's T-Test (P<=0.05).
Results presented as mean t standard deviation { N )
39
-------
Study Ho. 5221,06
TABLE 20
SUSCHROMIC TOXICITY OF ORTHO-CRESOL IK SPRAGUf OAULEY RATS
HALE ORGAN WEIGHT DATA (g)
{Terminal Sacrifice]
Organ
HEART
LIVER
SPLEEH
KIDHEY-LFT
JCIDNEY- RT
TEST1S-LFT
1EST1S-RT
ADRENALS
BRAIN
THY. /PARA.
0 ing/kg/day
1.677 i
17.609 t
0. 747 i
1.924 *
1.951 i
1.642 ±
1.669 *
0.053 i
2.132 t
0.030 t
0.15U
1.848<
0.104<
0.219(
0.23K
0.196<
0.1 2B(
0.011(
0.095C
0.010C
20)
20)
20)
20)
HO)
203
20)
20)
20)
20)
50 mg/kg/day
1.694 *
17.713 *
0.768 i
1.967 i
2.010 i
1.610 i
1.649 ±
0.054 t
2.159 t
0.030 ±
0.174<
2.679C
0.118C
0.228<
0.249<
0.34H
0.337C
0.009(
0,089(
0.009C
20)
20)
205
20)
20)
203
20)
20)
20)
20)
175 mg/kg/day
1.716 t
18.096 ±
0.755 ±
2.094 ±
2.085 t
1.730 t
1.729 *
0.054 t
2.189 t
0.031 t
0.17U
2.195C
0.093C
0.265C
0.256{
0.117C
0.109C
0.009(
0.08K
0.006C
20)
20)
20)
20)
20)
20)
20)
20)
20)
20)
600 mg/kg/day
1.595 ±
17.351 i
0.683 t
2.080 t
2.107 t
1.663 t
1.652 t
0.052 1
2.112 ±
0.031 ±
0.170C 12)
2.494C 12)
0.072( 12)
0.277C 12)
O.Z74< 12)
0.164( 12)
0.1 72< 12)
0.006( 12)
0.073< 12)
0.007C 12)
Results presented as mean ± standard deviation < N
40
-------
Study No. 5221.06
TABLE 21
SU8CHROMIC TOXICITY OF ORTHO-CRESQL IN SPRAGUE DAULET RATS
FEHALE ORGAN WEIGHT CATA (g)
[Terminal Sacrifice]
Organ
HEART
LIVER
SPLEEN
KIDNEY-LFT
KIDNEY-RT
OVARY -LFT
OVARY -RT
ADRENALS
BRAIN
THT./PARA.
0 mg/kg/day
0.917 t
8.295 i
0.492 ±
0.991 ±
1.023 t
0.042 *
0.042 i
0.062 t
1.968 ±
0.025 *
C.112<
0.770(
0.04Q<
0.122C
0.139C
0.018C
0.015C
0.010C
0.033C
Q.Q07C
205
20)
20)
205
20}
205
20}
20)
205
20}
50 mg/kg/day
1.039 ±
8.923 t
0.505 t
1.084 t
1.118 ±
0.041 ±
0.042 t
0.062 t
1.913 ±
0.023 t
0.145<
1.027C
0.070(
0.133<
0.149(
0.013t
0.01U
0.01U
0.285(
0.006<
205*
205
205
205
205
195
18)
205
195
205
175 mg/kg/day
0.952 t
8.603 *
0.517 t
1.037 ±
1.100 ±
0.043 ±
0.044 1
0.060 t
1,899 ±
0.025 ±
Q.12QC
1.113C
0.066(
0.1 28<
0.197C
0.012(
0.011C
0.011C
0.2S3C
0.006{
205
20)
205
205
205
205
205
20)
19)
20)
600 mg/kg/day
' 0.873 *
8.067 *
0.497 ±
0.944 ±
0.971 ±
0,046 i
0,033 ±
0.066 t
1.941 ±
0.026 ±
0.124C 45
0.734C 4)
0.104( 4}
0.090C 4)
O.OSZ( 45
O.OHC 45
0.012C 45
0.005C 45
0.01'C 45
0.006( 4)
* •• Statistically significant difference from control group
ysing ANOVA and Dunnett's T-Test (P<=0.055.
Results presented as mean i standard deviation < M 5
41
-------
'Table 22
Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
Clinical Chemistry Values
[Baseline!
Hales Females
T PBO 5.5 + 0.4 (10) 5.6 + 0.3 (10)
(g/dl)
ALB 3.5 + 0.2(103 3.7+0.4(10)
(g/dl)
GLOB 2.0+0.3(10) 1.9+0.5(10)
(g/dl)
ALB/GL08 1.8 + 0.3 (10) 2.2 + 1.1 (10)
(ratio)
BUM 10.7+1.8(10) 13.7+2.1(10)
(mg/dl)
T BIL 0.31 + 0.05 (10) 0.23 + 0.05 (10)
(mg/dl)
D BIL 0.08 + 0.06 (10) 0.05 + 0.04 (10)
(mg/dl)
GLU 66.0+9.3(10) 71.3+11,7(10)
(mg/dl)
CREAT 0.61 + 0.06 (10) 0.64 + 0.03 (10)
{mg/dl )
SGPT 41 + 8 (10) 40 + 7 (10)
(lu/D
SCOT 82+8 (10) 83+9 <10)
CHOL 68.0 + 13.5 (10) 75.4 + 10.0 (10)
(mg/dl)
ALK PKOS 226 + 49 (10) 186 + 38 (10)
CIu/l)
Results presented as mean + standard deviation (
42
-------
Table 23
Subchronie Toxfcity of Ortho-Cresol in Sprague Oawley Rats
Hematology Values
[Baseline]
Hales Females
SBC 7.04 + 0.65 (10> 6,84 + 0,38 <10>
(x 1(
HGS 14. S + 1.1 (10) 14.5 + 0.5 (10)
HCT 43.6+3.2(10) 42.0+1.6(10)
«)
me 15.5 + 3.0(10) 11.6 + 3.0(10}
(x
SECS 1.7+0.9(10) 0.9+0.5(10}
(x 10A3/imr3>
BANDS 0.0 + 0.0 (10) 0.0 + 0.1 (10)
(x 1
LYMPHS 13.4 + 2.8 (10) 10.3 + 2.5 (10)
(X 1
MONO 0.3 + 0.2 (10) 0.3 + 0.2 (10)
(x 1
EOS 0.1*0.2(10) 0.0 + 0.1(10)
(x 1
RETIC 1.1+0.5(10) 1.5+0.7(10)
<% R8C)
Results presented as mean + standard deviation ( N
43
-------
QUALITY ASSURANCE STATEMENT
Study Title: Subchronic Toxicity of Ortho-Cresol in
Sprague Dawley Rats
Study Number: 5221.06
Study Director: L. Thomas Mulligan, Ph.D.
Initiation Date: September 16, 1985
Review Completed Date: January 9, 1987
This study has been divided into a series of phases. Using a
random sampling approach, Quality Assurance monitors each of
these phases over a series of studies. Procedures, documenta-
tion, equipment, etc., are examined in order to assure that the
study is performed in accordance with the U.S. FDA Good
Laboratory Practice regulations {21CFR58), the U.S. EPA GLPs
(40CFR792 and 40CFR160), and the OECD guidelines and to assure
that the study is conducted according to the protocol.
The following are the inspection dates, phases inspected, and
report dates of QA inspections of this study.
Microbiological Associates, Inc,
-------
DATES/PHASES
INSPECT OH 85/09/27 - 85/09/27,TO STUDY DIE 85/09/27,TO MCMT 85/09/27
PHASES: PROTOCOL REVIEW
INSPECT ON 85/11/12 - 85/ll/12,TO STUDY DIE 85/11/12,TO MGMT 86/01/03
PHASES: BODY WEIGHTS
ANIMAL OBSERVATIONS
INSPECT ON 86/04/07 - 86/04/10,TO STUDY DIR 86/04/10,TO MGMT 86/08/15
PHASES: DATA REVIEW
INSPECT ON 86/08/04 - 86/08/07,TO STUDY DIR 86/08/07/TO MGMT 86/08/15
PHASES; DRAFT REPORT
INSPECT ON 87/01/07 - 87/01/07,TO STUDY DIR 87-/01/07,TO MGMT 87/01/09
PHASES': DRAFT TO FINAL REPORT
-Microbiological Associates, Inc.
-------
This report describes the methods and procedures used in the
study and the reported results accurately reflect the raw data
of the study.
Quality Assurance Date
RA/QA Department
-Microbiological Associates, Inc,
-------
Study No. 5221.06
APPENDIX A
TWO-WEEK RANGE-FINDING/EXPICiRATORY STUDY OF ORffiO-CRESOL
IN SPRAGUE BAWLEY RATS
-------
-------
Study No. 5221.06
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
MALE BODY WEIGHT DATA (g)
TEST
DAY
DAY 1
DAY 8
DAY 14
0 mg/kg/day
160.2 i 5.1(
219.1 t 6.0C
271.6 t 10. 9(
10)
105
10)
5 ng/kg/day
153.8 t 7.4{
Z13.4 * 11. 7(
265.0 ± 19. 7(
10)
10)
10)
10 mg/kg/day
154.4 * 5.6{
214.9 ± 14. 5<
267.0 t 21 .3(
10)
10)
10)
25 mg/kg/day
154.4 t 7.7{
218.0 t 19. 4{
275.7 ± 30. B(
10)
10)
10)
50 mg/kg/day
158.4 t 7.5{ 10)
221.5 t 10. 2{ 10)
278.5 ± 20.3C 10)
100 mg/kg/day
156.4 * 4.5(
214. 9 * 12. 7{
262.5 t 21 .9(
10)
9>
9)
Results presented as mean * standard deviation ( N )
-------
-------
Study No. 5221.06
l
U!
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE BODY WEIGHT DATA (g>
TEST
DAT 0 mg/kg/day 5 mg/kg/day 10 mg/kg/day 25 mg/kg/day 50 mg/kg/day 100 mg/fcg/day
DAT 1 116.2 ± B.1< 10) 117.6 t 5.4( 10) 118.5 i 10.2( 10) 118.1 ± 10.5( 10) 119.4 ± 5.B( 10) 117.2 i 7.0( 10)
DAY 8 164.1 i 9.8( 10) 163.9 ± 9.01 10) 159.8 ± 10.2( 10) 162.2 t 13.6( 10) 165.2 t 10.5( 10) 162.1 ± 12.U 10)
DAY 14 191.6 ± 10.3(10) 192.0* 11.8(10) 190.2* 13.5(10) 191.5 t 16.0(10) 192.7 t 11.9(10) 191.2* 15.7(10)
Results presented as mean 1 standard deviation ( N )
-------
Study No. 5221.06
TWO WEEK RANGE-FIND ING/EXPLORATORY STUDlf OF ORTHO-CRESQL IN SPRAGUE DAWLEV RATS
MALE FOOD CONSUMPTION DATA (g/day)
TEST
WEEK 0 ing/kg/day 5 mg/kg/day 10 mg/kg/day 25 mg/kg/day 50 mg/kg/day 100 mg/kg/day
yEEK 1 21.9 t 1.9{ 10) 23.1 * 4.5( 10) 22.6 t 3.2( 10) 22.1 t 3.2< 10) 23.5 t 2.4( 10) 20.8 t 4.9( 10)
WEEK 2 25.5 t 2.4( 10) 25.6 l 2.8( 10) 25.5 t 3.3{ 10) 27.3 * 4.9C 10) 26.4 t 3.9( 10) 25.7 l 2.3( 9)
Resutts presented as mean t standard deviation ( N )
-------
Study No. 5221.06
TWO WEEK RANGE-FIHOI NO/EXPLORATORY STUDY OF ORTHO-CRESOL IN SPRAGUE OAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (g/day)
TEST
UEEK 0 mg/kg/day 5 mg/kg/day 10 mg/kg/day 25 mg/kg/day 50 mg/kg/day 100 mg/kg/day
WEEK 1 19.8 t 4.4( 10) 17.8 t 1.6( 10) 18.3 t 1.9( 10) 20.0 ± 4.5< 10} 19.6 * 3.3( 10) 18.4 * 2.9( 10}
WEEK 2 25.0 ± 9.6( 10) 19.7 t 1.9( 10) 23.S t 9.2{ 10) 22.0 ± 4.9( 10) 24.6 ± 8.2( 10) 22.8 t 6.1C 10)
Results presented es mean t standard deviation ( N )
-------
TWO WEEK RANGE-HNDING/EXPLQRATQRY STUDY OF ORTHO-CRiSOL IN SPRACUE DAWLEY SATS
KALI SOOY WEIGHT DATA (g)
ANIMAL NUMBER DAY 1 DAY 8 DAY 14
DOSE LEVEL
0 mg/kg/day
5 rng/kg/day
10 mg/kg/day
25 mg/kg/day
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
2176
2177
2178
2179
2180
2181
2182
2183
2184
2185
21 66
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
2198
2199
2200
161.9
164.2
160.8
154.5
166.8
158.2
152.7
160.3
155.1
167.5
163.7
153.1
143.1
142.7
148.9
152.8
156.2
157.1
155.8
164.2
161.1
154.9
150.9
165.1
154.1
145.9
157.7
149.8
151.7
152.6
156.4
150.6
159.4
141.5
144.2
162.9
150.6
165.0
158.6
154.9
227.1
211.3
216.6
213.8
220.2
225.1
210.4
221.7
219.4
225.6
223.5
222.8
208.2
192.1
207.6
210.6
222.7
208.7
205.7
232.1
220.3
222.7
224.1
235.7
220.0
198.6
215.4
217.2
183.9
211.1
213.6
199.8
245.3
194.7
202.4
245.3
234.0
199.1
229.5
216.4
2S6.8
257.1
255.5
265.5
274.7
280.6
261.6
281.5
277.3
275.6
288.1
275.0
263.1
229.8
250.7
270.9
276.5
254.0
248.1
294.1
271.3
273.9
277.7
301.3
279.1
250.1
260.7
276. D
220.8
259.6
242.5
267.6
325.6
244.3
254.9
312.9
299.4
243.6
296.4
269.6
A-6
-------
MEEK RANGE-FINDING/EXPLORATORY STUDY Of QRTHQ-CRESOL IH SPRAGUE DAMLEY RATS
MALE BODY yglGHT DATA
-------
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CiESOL IN SPRAGUE DAULEY RATS
FEMALE'BODY WEIGHT DATA (g)
ANIMAL NUMBER DAY 1 DAY 8 DAY 14
DOSE LEVEL
0 mg/kg/day
5 mg/kg/day
10 mg/kg/day
25 mg/kg/day
2221
2222
2223
2224
2225
2226
2227
2223
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
103.5
113.9
107.9
116.1
116.3
117.8
121.5
109.6
130.2
125.5
118.9
107.9
111.2
123.6
114.0
119.9
116.3
117.0
123.6
123.6
112.6
110.4
135.4
126.8
132.5
114.9
110.9
122.0
104.9
114.4
110.2
127.1
113.9
128.6
109.8
110.2
124.9
109.5
137.7
109.1
152.6
152.2
157.1
168.7
169.4
167.3
170.9
152.1
179.5
170.9
170.2
145.3
155.5
165.9
165.5
161.1
161.9
163.8
171.8
177.6
161.0
152.7
148.5
172.6
180.2
147.4
159.2
160.1
155.0
161. S
147.8
161.1
165.5
174.3
150.8
152.1
171.6
191.0
153.5
154.0
175.0
178.6
191.4
195.0
199.3
196.1
200.5
179.1
204.7
196,0
205.2
170.4
182.9
1S6.7
197.5
188.7
192.8
184.1
208.1
203.4
189.3
182.2
190.9
205.6
215.8
165.0
189.8
189.4
183.7
190.4
179.1
192.5
192.2
208.8
181.2
174.0
198.7
224.3
174.3
190.0
A-8
-------
TWO WEEK RANGE-FIND I KG/EXPLORATORY STUDY OF QRTHQ-CRESOl IN SPRAGUE DAyiEY RATS
FEMALE'BODY WEIGHT DATA Cg)
ANIHAL NUMBER DAY 1 DAY 8 DAY 14
DOSE LEVEL
50 mg/kg/day
100 mg/ks/day
2261
2262
2263
2264
2265
2266
2267
2268
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
22BO
121.5
111.4
112.5
127.6
122.4
122.5
122.1
117.8
111.5
124.4
109.0
111.9
126.3
121.7
121.9
125.7
116.0
106.0
120.2
113.2
162.3
147.8
165.2
173.4
172.8
172.4
169.4
161.7
H8.2
178.9
149.2
160.6
1B0.6
178.0
159.1
175.2
160.6
144.8
155.4
158.0
196.8
172.0
198.4
201.8
201.5
202.7
192.3
186.9
172.4
201.8
177.7
190.6
210. 7
205.7
192.6
212.4
189.1
161.2
182. 6
189.5
A-9
-------
TWO MEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHQ-CRESQL IN SPRAGUE DAWLEY RATS
HALE FOOD CONSUHPT10N DATA (g/dayj
ANIMAL NUMBER UEEK 1 WEEK 2
DOSE LEVEL
0 mg/kg/day
5 nig/kg/day
10 mg/kg/day
25 mg/kg/day
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
2176
21 77
2178
2179
2180
2181
2182
2183
2184
2185
2186
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
2198
2199
2200
24.2
18,5
19,4
21.6
22.1
'21.5
21.9
21.5
24.9
23.1
22.9
23.9
20.7
18.0
22.6
34.8
20.7
21.4
22.4
23.7
22.6
21.2
22.5
22.9
24.9
17.5
28.7
22.9
18.1
24.5
20.6
17.4
28.1
19.1
22.2
25.8
21.0
20.1
24.2
22.9
27^0
20.8
22.4
26.4
26.7
24.2
25.2
26.7
28.2
27.5
27.6
27.5
24.1
20.2
26.9
27.1
26.4
26.1
21.6
28.7
27.2
25.3
25.8
30.4
27.6
21.9
23.4
25. S
19.1
28.6
24.3
22.5
34.6
23.7
28.0
35.8
29.3
21.3
28.3
25.5
A-10
-------
TWO WEEK RANCE-F1NDINC/EXPLORATORY STUDY OF ORTKQ-CRESOl IN SPRAGUE 0AWLEY RATS
MALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NUMBER WEEK 1 MEEK 2
DOSE LEVEL
50 mg/kg/day 2201
2202
2203
2204
.2205
2206
2207
2208
2209
2210
100 mg/kg/day 2211
2212
2213
2214
2215
2216
2217
2218
2219
2220
21,5
22.2
24.4
28.1
25.7
20.6
26.3
22.7
21. §
22.2
27.7
19.6
21.2
22.8
21.4
22.9
24.5
17.8
21.0
9.1
22.5
25.4
23.3
35.4
26.6
24.5
30.4
26.4
23.9
25.3
25.4
24.5
25.4
23.0
25.1
27.7
28.8
22.5
28. 9
na
na = no data available.
A-ll
-------
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESQL IN SPRAGUE DAULEY RATS
MALE FOOD CONSUMPTION DATA (g)
CFeeder Ueightsl
ANIMAL NUMBER new feeder 1 old feeder 1 new feeder 2 old feeder 2
DOSE LEVEL
0 mg/kg/day
5 mg/kg/day
10 mg/kg/day
25 mg/kg/day
2161
2162
2163
2164
2165
2166
2167
2168
2169
2170
2171
2172
2173
2174
2175
Z176
2177
2178
2179
2180
2181
2182
2183
2184
2185
2186
2187
2188
2189
2190
2191
2192
2193
2194
2195
2196
2197
219S
2199
2200
490.3
518.9
512.7
483.7
504.0
447.1
498.7
403.5
475.3
506.9
507.7
508.4
539.7
468.1
469.7
451.0
499.5
465.6
495.6
475.9
490.8
513.7
512.2
521.4
507.3
460.4
575.7
461.1
475.4
485.0
495.2
509.2
457.3
520.4
519.8
506.6
495.6
505.6
499.7
531.4
320.6
389.2
376.9
332.5
349.4
296.5
345.1
252.7
301.3
345.3
347.3
340.8
395.1
341.8
311.6
207.3
354.3
315.8
339.0
310.2
332.4
365.3
354.6
361.0
333.2
338. 2
374.5
300.7
348.6
313.6
351.3
387.1
260.6
386.6
364.3
325.9
348.9
364.6
330.2
371.4
457.6
551.4
564.1
530.4
519.2
478.6
497.4
449.2
509.6
498.1
539.2
520.6
598.5
481.7
491.1
471.4
553.8
537.9
525.4
481.4
510.3
524.9
510.0
521.4
505.8
537.5
530.0
493.4
510.0
514.7
545.8
560.4
450.6
526.9
532.6
495.0
496.7
499.1
510.8
500.1
295.7
426.7
429.7
372.0
359.0
333.6
346.2
289.0
340.7
333.4
373.8
355.7
454.1
360.5
329.9
308.9
395.2
381.3
395.5
309.4
347.3
373.2
355.2
338.9
340.0
405.9
389.7
338.6
395.2
343.2
400.0
425.2
242.9
384.5
364.6
280.2
321.2
371.2
340.8
347.2
A-12
-------
TWO WEEK SANGE-FINDING/EXPLORATORT STUDY OF ORTHQ-CRESQL IN SPRAEUE DAULEY RATS
MALE FOOD CONSUMPTION DATA £g)
[Feeder Weights]
ANIMAL NUH8E8 new feeder 1 old feeder 1 new feeder 2 old feeder 2
DOSE LEVEL
50 nig/ kg/day 2201
2202
2203
2204
2205
2206
2207
2208
2209
2210
100 mg/fcg/day 2211
2212
2213
2214
2215
2216
2217
2218 "
2219
2220
504.7
500.3
516.7
448.5
499.6
532.6
526.0
485.9
504.9
521.5
519.6
522.9
510.5
513.0
543.7
501.8
537.8
543.9
496.7
484.5
354.4
344.7
345.9
251.5
319.9
388.6
341.6
327.0
352.2
366.1
325.7
386.0
362.3
353.6
394.1
341.3
366.4
419.1
349.8
420.9
508.5
493.6
513.9
443.6
501.0
543.8
500.1
455.6
499.6
507.4
509.3
532.7
480.3
522,1
540.8
478.6
510.4
539.3
487.4
na
373.6
341.3
374.3
231.0
341.7
396.5
317.6
297.0
356.0
355.5
356.7
385.6
327.9
384.0
390.4
312.6
337.6
404.3
313.9
na
na = no data available.
A-13
-------
TWO UEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESOL IN SPRAGU6 OAWIEY RATS
FEMALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NUMBER UEEK 1 WEEK 2
DOSE LEVEL
0 ing/kg/day
5 mg/kg/day
10 mg/kg/day
25 mg/kg/day
2221
2222
2223
2224
2225
2226
2227
2228
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249-
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
17.6
31.8
17.1
19.2
19.2
18.6
20.1
16.2
19.3
19,2
18.8
17.3
16.5
16.5
19.2
15.5
17.5
18.1
17.9
20.9
21.4
17.9
16.1
17.9
19.5
15.6
17.1
20.8
18.0
18.4
1B.7
16.5
16.8
18. 8
17.8
16.3
24.2
31.0
20.0
19.5
17.1
19.4
20.6
19.3
37.1
30.8
21.3
45.6
19.2
19.4
20.8
18.3
17.9
17.9
22.0
18.6
20.2
17.4
21.3
22.7
32.1
23.7
46.9
19.5
21.6
15.4
19.9
18.7
21.3
19.4
20.9
20.7
19.2
20.4
19.4
17.6
34.2
26.0
18.4
23.2
A-14
-------
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY Of ORTHO-CSESOL IH .SPRAGUE 0AULEY RATS
FEMALE FOOD CONSUMPTION DATA (9/day)
ANIMAL NUMBER WEEK 1 WEEK 2
DOSE LEVEL
50 mg/kg/day
100 mg/kg/day
2261
2262
2263
2264
2265
2266
2267
2266
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
2280
22.3
16.5
17.9
IB. 7
20.0
28.0
18.5
17.9
17.5
18.9
16.7
17.5
24.5
21.6
16.0
18.9
19.7
15.3
15.3
18.4
23.4
18.7
23.5
ZQ.5
22.9
35.7
20.2
43.0
17.8
20.3
21.0
18.2
25.7
35.7
19.7
20.7
29.7
15.4
18.8
23.5
A-15
-------
TWO WEEK RANGE-FlNDtNG/EXPlORATQRY STUDY OF CRTHO-CSiSQL IN SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (g>
[Feeder Weights]
ANIHAI NUMBER ne« feeder 1 old feeder 1 new feeder 2 old feeder 2
DOSE LEVEL
0 mg/kg/day
5 mg/kg/day
10 aig/ kg/day
25 mg/kg/day
2221
2222
2223
2224
2225
2226
2227
2228
2229
2230
2231
2232
2233
2234
2235
2236
2237
2238
2239
2240
2241
2242
2243
2244
2245
2246
2247
2248
2249
2250
2251
2252
2253
2254
2255
2256
2257
2258
2259
2260
513.2
516.9
547.5
516.8
513.3
529.8
517.7
529.4
524.7
498.4
501.6
516.9
538.3
521.8
547.4
510.6
506.6
572.2
536.3
512.6
491.9
438.4
513.4
532.5
551.8
545.7
520.4
562.2
497.9
544.9
508.1
524.6
532.0
506.9
534.8
530.5
463.6
516.9
560.9
535.9
390.1
294.1
427.6
382.2
378.8
399.8
376.7
415.9
389.6
364.2
370.1
395.9
422.9
406.1
413.3
401.9
384.3
445.5
410.8
366.3
342.1
362.8
400.7
407.3
415.4
436.8
400.4
416.5
372.1
416.0
376.9
409.1
414.3
375.3
410.2
416.5
294.5
300.1
421.2
399.4
529.1
457.0
561.1
515.7
535.6
541.2
503.2
538.1
511.8
474.5
483.0
533.5
519.9
491.7
508.4
516.3
527.3
549.2
558.4
488.4
422.7
467.3
518.5
510.4
498.4
516.9
494.4
524.8
483.4
524.1
484.1
509.0
546,2
492.3
502.2
563.3
423.9
414.3
545.6
529.5
426.5
340.4
437.4
400.1
313.0
356.7
375.7
264.5
396.7
358.1
358.2
423.7
412.6
384.2
376.1
404.5
406.2
445.0
430.5
352.0
230.4
324.9
236.9
393.5
368.7
424.7
374.8
412.4
355.4
407.7
358.8
384.7
431.0
370.0
385.8
457.8
218.6
259.1
435.3
390.2
A-16
-------
TWO WEEK RANGE-FINDING/EXPLORATORY STUDY OF ORTHO-CRESOL IN SPRACUE DAUIEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NUMBER new feeder 1 old feeder 1 new feeder 2 old feeder 2
DOSE LEVEL
50 mg/kg/day
100 mg/kg/day
2261
2262
2263
2264
2265
2266
2267
2263
2269
2270
2271
2272
2273
2274
2275
2276
2277
2278
2279
2280
425.1
426.4
538.8
525.2
471.5
503.8
516.1
523.4
442.3
563.7
510.6
433.1
558.0
521.4
485.4
510.9
544.3
468.3
501.9
538.2
268.9
310.6
413.4
394.3
331.7
307.6
386.7
398.4
320.0
431.4
393.5
360.6
386.6
370.5
373.5
378.8
406.4
361.4
395.1
409.2
387.0
411.8
520.7
498.3
459.7
417.8
465.2
495.8
427.7
537.5
485.1
474.5
487.2
469.5
487.6
473.5
493.7
445.6
473.5
490.0
246.9
299.7
379.8
' 375.3
322.4
203.4
344.2
237.6
320.9
415.6
359.2
365.3
333.3
255.6
369.2
349.5
315.7
353.1
361.0
349.1
A-17
-------
-------
Study No. 5221.06
APPENDIX B
ANALYTICAL CHEMISTRY 14ETHODOLOCT
B - 1
-------
-------
AMERICAN BIOGENIC5 CORPORATION
ANALYTICAL REPORT
PROJECT NO.8
SUBJECT:
//-fit d
». tr *
^U/
*
PAGE
DATE
Z6IOOOG
OF J
3
DEPARTMENT NO. 440
TEST ARTICLE NO. : ~"
99?*
*
TECHNICIAN
REVIEWED BY
ff
Reproduced Irom
best available copy.
DATE
B-2
-------
-------
American Biogenics
Corporation
March 26, 1986
Dennis D. Dietz, Ph.D.
Technical Program Monitor
Research Triangle Institute
P.O. Box 12194
Research Triangle Park, NC 27709
Dear Dennis:
Results
below:
SAMPLE ID
for the o-cresol confirmatory analyses are
(units mg/ml)
DILN FACTOR
DILUTION 1
DILUTION 2
tabulated
MEAN
C0161A85
C0164A85
C0185A85
C0186A85
C0256A85
C0257A85
C0502A85
C0505A85
C0587A85
C0617A85
C0627A85
C0658A85
C0744A85
C0834A85
C0957A85
C0974A85
100
10,000
2,500
10,000
2,500
10,000
100
10,000
100
100
10,000
10,000
10,000
5,000
10,000
2,500
0
124.7
37.89
130.6
37.89
129.6
0
127.3
0
0
129.9
134.6
127.1
38.8
127.7
36.7, 37.6
0
129.9
38.12
130.6
37.65
133,5
0
125.8, 126.8
0
0
130.8
135.5
125.2
39.0
130.6
36.2
0
127.3
38.0
130.6
37.8
- 131.6
0
126.6
0
0
130.4
135.1
126.2
38.9
129.2
36.9
The analysis was done on a Perkin Elmer 400 HPLC equipped with
a Model 95 UV-VIS spectrometer set at 221 run. The separation was
effected on an IBM 250mm slica column {S/N 2002037) at a flow rate
of 2.0 ml/nun of 1% isopropanol/99% hexane. A 10 uL injection loop
was used for injection.
B - 3
(2171875-3930 « Telex: 250139 « 1BQOE. Pershing Rd •DscaJyr, IL 62526
-------
-2-
Enclosed for your information is a sample of the analysis
tracing.
Sincerely yours,
Edwin A. Wool son, Ph.D.
Manager, Analytical Chemistry
EAWinssd
Enclosure
B - 4
-------
\\v
..__j_
r-
-o
F
. , ^. ,.,^... ....^... -___!£'—-;--
Reproduced from
best available copy.
-------
RCO
L. I
ENSECO
June 2, 1986
Dr. Dennis D, Diets
Research Triangle Institute
? .0. Sox 12194
Research Triangle Park, NC 277Q9
Dear Dennis ;
Enclosed please find a description of the method we use for
analysis of compounds by direct aqueous injection as it pertains
to work perforaed under SPA WA-35.
As you can see, the analysis procedure is generally the
same for all compounds differing only in the case of the cresols
which use an alternate column and temperature program,
If you have any questions regarding the method or other
specifics, please do not hesitate to contact me.
Sincerely,
W . Henry Camp
Analytical Chemist
VOA Laboratory
WHC:mk
Encl.
cc: Dr. Barry Levins (Microbiological Associates)
Dr. Dale Mayhew (American 3iogenics Corp.!
Dr. Crosby Thompkins (Toxieity Research Laboratories
B-6
-------
This method covers the determination of compounds by direct
aqueous injection. The following co-impounds can be detected
using column A, and temperature program A: acetone, methyl
isobutyl ketone (MI3K), isobutyl alcohol, methyl alcohol, ethyl
acetate, n-butyl alcohol and crotonaldehyde. The following
compounds can be detected using system B and temperature
program B: p-, m-, and o-cresol.
2. Summary.
A portion of a sample is injected directly onto a ges
ehromatograph capillary column. The gas chromatograph is
temperature programmed "to separate the constituents which are
then detected by a flame ioniaation detector.
3. Instrumentation and Apparatus.
3.1. Gas ehromatograph -- Hewlett-Packard 5880 with auto-
sampler and integrator. Oven temperature profile A
programmed as hold 8 min at 50'C, then to 220°C at
8 "C/in in and hold 5 min. Program B: hold 5 oin at
50°C then to 25Q"C at 10'C/rain and hold 15 min.
3.2. Column A — 60 m x 0.32 mm ID, 0.25 ym film SUPEL-
COWAX 10 fused silica capillary column'. Set linear
velocity to 25 cni/sec, Ke, at iOO'C (flow rate = 1.2
ml/min } .
Column B -- 30 m x 0.318 mm ID, 0.25 urn film SE - 54
fused silica capillary column. Set linear velocity
B-7
-------
to 25 cm/sec, He, a* 100*0 (flow rate
3.3. Injector -- configure for sample splitting and ad-
just' ratio to 100:1, Set heater temperature to
200'C.
3.4. Detector -- Hewlett-Packard flame ionization de-
tector. Hydrogen flow set at 40 ml/min. Air flow
set at 400 ml/sin. Set sensitivity at 2*2 and ad-
just if necessary. Set heater temperature to
25C'C.
3.5. Syringes -- 1 ml, 100 ul, and 10 yl gas-tight glass
for diluting and for sample transfer.
4. Reagents.
4.1. Reagent Water -- prepare with Corning Mega-Pure dis-
tillation system and filter through activated
charcoal prior to use.
4.2. Methylene Chloride -- J. T. Baker "Resi-analyaed" or
equivalent.
4.3* Standard Solution -- prepare "by adding pure material
to water. Pure material should "be assayed reference
liquid such as Chera Serve reagents. If not immedi-
ately available, supplied compound may be used.
4,3.1. Place about 9 ml of solvent into a stoppered 10 nil
flask. Weigh the flask. Add one or two drops of
pure material to the flask and reweigh. Dilute to
B-8
-------
volume, mix well, and siore In a teflon-sealed
screw-eao vial at 4 ° C .
5 . Calibration.
'5.1. External Standard Calibration -- Prepare working
standards to bracket the concentration range, of the
samples of interest. Working standards are prepared
by diluting the standard solution with water or
raethylene chloride if the samples are corn oil
based. Analyze according to procedure section then
calculate response factors using this equation:
concentration of standard
area of standard
If the response factors are constant over the
working range (10/5 Relative Percent Difference), an
average response factor may be used for calcu-
lations .
6. Quality Control.
6.1. Interference -- a water blank must be run with each
test to check for system contamination. A blank
should also be run between samples of high concen-
tration .
6.2 Purity -- reagents used in the procedure should also
be analyzed with each test to determine their
purity,
B-9
-------
6,3 Spikes -- sample matrixes should be spiked svith ihe
compounds of interest and a percent recovery calcu-
lated to access matrix effects and method, accuracy.
6.4. Duplicates -- Some samples should be analysed in
duplicate and a relative percent difference calcu-
lated to access method precision.
7 , Procedure.
7.1. Calibration as in section 5.
7.2, Sample Preparation -- allow samples to come to room
temperature before handling. , Dilute if necessary to
bring concentrations within system working range by
adding portion of sample to water or to methylene
chloride if corn oil based.
7.3- Analysis -- introduce sample by direct injection of
1 - 2 yl into the GO injection port and begin the
temperature program.
7.4 Identification -- as the compounds are analyzed
individually, there should be no coelution inter-
ferences. Retention time should still be checked
against the standard.
3 . Calculation.
8,1. Concentration -- calculate using peak area and RF
determined in section 5.1.
B-10
-------
5,2. Dilution -- take into account any dilution performed
on the sanple or the standard.
8.3 Report results in mg/ml without correction for
recovery percentage.
B-ll
-------
-------
Study No. 5221.06
APPENDIX C
CLINICAL PATHOLOGY METHODOLOGY
C-l
-------
-------
HEMATOICGY
Hemoglobin
Cyanmethejitoglobin method
Baker Cell Counter
Hematorcgy Series 7000
Hematocrit
Indirect method; calculated value based on erythrocyte
count and mean corpuscular volume
Baker Cell Counter
Hematology Series 7000
Eryttoocyte Count
Electronic Counting Procedure
Baker Cell Counter
Hematology Series 7000
Mean Corpuscular Volume fMCVl
Electronic Sizing Procedure
Baker Cell Counter
Heniatology Series 7000
Mean Corpuscular Hemoglobin fMCH)
Indirect method; calculated value based on erythrocyte
count and hemoglobin
Baker Cell Counter
Hematology Series 7000
Mean Corpuscular Hemoglobin Concentration MCHC)
Indirect method; calculated value based on hematocrit
and hemoglobin
Baker Cell Counter
Hematology Series 7000
Leukocyte Count
Electronic Counting Procedure
Baker Cell Counter
Hemtology Series 7000
C-2
-------
-------
Leukocyte Differential Count
Neutrophils - Immature (bands)
Neutroph'ils - Mature (segs)
Mbnocytes
Easophils
Lymphocytes ,"
Ecsinophils
Wright stain procedure
Schaljn, O.w. , Jain, N.c. and Carroll, E.J.
Veterinary Hematology, Color Plates Chapter,
3rd Edition, Lee and Feblger, 1975.
Count
New methylene blue staining procedure
Brecher, G, Am. J. din. Path. 19,
895, 1949.
ProthrcsT'bin Time (FT)
Rate of change in absorbance due to clot formation
Coag-A-Mate
Activated. Partial_Thrgmboplastiri Time (AFTT)
Rate of change in absorbance due to clot formation
Coag-A-Mate
CT.THICAL CHEMISTRY
Creatinine
Jaffa's alkaline picrate reaction
Centrifichem Centrifugal Analyzer System
Fabiny, D.L. and Ertingshausen, G.
Clin. Chera., 12, 696, 1971.
Ino_rganic_Phosphorus
Phosphomolybdate reaction
Centrifichem Centrifugal Analyzer System
Daly, J.A., and Ertinghausen, G.
Clin, Chem., 18, 263, 1972.
C-3
-------
Glucose
Hexokinase method'
Centrifichem Centrifugal Analyzer System
Bcndar, J.L. and. Mead, D.C.
Clin. Chan. 20, 586, 1974.
Urea Nitrogen (BUN)
Modified urease technique
Centrifichem Centrifugal Analyzer System
Talke, H. and Schubert, G.E.
Klin. Wchnschr. 43, 174, 1965.
Biuret technique
Centrifichem Centrifugal Analyzer System
Kingsley, G.R. , J. Biol. Chem. 131, 197, 1939.
Albumin
Brcmocresol Green method
Centrifichem Centrifugal Analyzer System
Doumas, B.T. and Biggs, E.G.
Standard Methods of Clinical Chemistry, 7, 175, 1972,
Globulin
Total Protein - Albumin = Globulin (Calculated value) .
Calcium.
Modified alizarin procedure
Centrifichem Centrifugal Analyzer System
Frings, C.S., et. al., Clin. Chem. , 16, 816, 1970.
Aspartate Amino Transferase (AST/SCOT)
Modified Karmen procedure
Centrifichem Centrifugal Analyzer System
Bergmeyer, H.V. , Scheibe, P., and Wahlefeld, A.W.
Clin. Chem., 24, 58, 1978.
Alanine Ami-no_Transferase (AUT/SGPT)
Modified Henley & Pollard procedure
Centrifichem Centrifugal Analyzer System
Bergmeyer, H.V. , Scheibe, P., and Wahlefeld, A.W.
Clin. Chem., 24, 58, 1978.
C-4
-------
Alkaline Phosphatase
Modified Bowers-McComb procedure
Centrifiehem Centrifugal Analyzer System
Bowers, Jr., G.N., McComb, R.3.
Clin. Chem,, 12, 70, 1966.
Cholesterol
Allain enzymatic procedure
Centrifichem Centrifugal Analyzer System
Allain, C.C., et. al., Clin. Chem. 20, 470, 1974.
Total, Bilirubin
Diazo colorimetrie procedure
Centrifichem Centrifugal Analyzer System
Ertinghausen, G., Fabiny-Byrd, D.L., Tiffany, T.O.,
and Carey, S.J., Clin. Chem. JL9, 1366, 1973.
Direct Bilirubin
Diazo colorimetric procedure
Centrifichem Centrifugal Analyzer System
Ertinghausen, G., Fabiny-Byrd, D.L., Tiffany, T.O.,
and Carey, S.J., Clin. Chem. 19, 1366, 1973.
Electrolytes (Na+, K4", Cl~, C02)
Ion specific electrodes (Metpath, Inc.)
URINALYSE5
pualitative Measureirients
pH Ketones Urobilinogen
Protein Bilirobin
Glucose Blood
Chemstrip 7L - Chemistry Reagent Strips
BicHDynamdcs/brnc
Indianapolis, Indiana
C-5
-------
Specifig_ Gravity
Optical temperature compensated refractometer
Microscopic Evaluation
Urinary sediment stained with. Sedi-stain am evaluated using the Ames
Atlas of Urine Sedjjtient, Ames Co., Division Miles Laboratories, Elkhart,
Indiana.
C-6
-------
Study No. 5221.06
APPENDIX D
INDIVIDUAL ANIMAL DATA
D-l
-------
-------
Study No. 5221.06
DISPOSITION OF ANIHALS IN 13-WEEK ORTHO-CRESOL STUDY IN SPRAGUE DAWLEY RATS
Pi
Dose Level
(mg/kg/day)
0
50
175
600
0
50
175
600
Sex
H
M
H
H
f
F
F
F
Unscheduled Sacrifice3
9/27/85
2911-2913
2944-2946
2977-2979
3010-3012b
3043-3045
3076-3078
3109-3111
3142-3144b
45 -Day Sacrifice
10/31/85, 11/1/B5
2881-2890
2914-2923
2947-2956
2980-2989°
3013-3022
3046-3055
3079-3088
3112-3121°
90-Day Sacrifice
12/16 - 12/18/85
2891-2910
2924-2943
2957-2976
2990-3009d
3023-3042
3056-3075
3089-3108
3122-3141d
8 Initially to be used for neurotoxic testing, but this phase eliminated from study.
b Early deaths, animal numbers 3010, 3012, 3143.
c Early deaths, animal numbers 2984, 3112, 3113, 3121.
d Early deaths, animal numbers 2992, 2993, 2995, 2997, 3000, 3D04, 3006, 3008, 3122-3129, 3131-3134,
3137, 3138, 3140, 3141.
-------
-------
Study No. 5221,06
SUBCHRONIC TOXECITY OF OHmO-CRESOL
IN SERAGUE DftKLSY RAIS
ABHSEVIMION CODES
Body Weights and Food Consumption
ISAC - interim sacrifice
na - no data available
dead - unscheduled death
OrganWeights
na - no data available
dead - unscheduled death
tbw - terminal body weight
Urinalysis
c - clear
cl - cloudy
hz - hazy
y - yellow
py - pale yellow
ly - light yellow
a - amber
dy - dark yellow
s - straw color
tp - triple phosphate
co - calcium oxalate
ap - amorphous phosphate
n - none
tr - trace
m - aany
f - few
ng - negative
nr - normal
mod - moderate
nura - 'numerous
Hematology & Clinical Chemistry
QNS - quantity not sufficient
dead - unscheduled death
z - no clot was formed
thy./para. - thyroid/parathyroid
rt - right
1ft - left
occ - occasional
> - greater than
dead - unscheduled death
app - appearance
vol - volume
uro - urcibilinogen
bili - bilirubin
ery - erytiirocyfces
KBC/HPF - number of red blood cells
under high power field
WBC/HPF - number of white blood cells
under high power field
Casts/tPF - number of casts under low
power field
EPI/HPF - number of epithelial cells
cells under high power
field
D-2
-------
-------
SU8CHRONIC TOX1CITY OF ORTHO-CRESOL IN SPRAGUE DAWlEY RATS
HALE BODY WEIGHT DATA (g>
DOSE LEVEL
0 mg/kg/day
ANIMAL NO. WEEK 1 UEEK 2 WEEK 3 UEEK 4 WEEK 5 WEEK 6 UEEK 7
50 mg/kg/day
2881
2B82
2883
2884
2885
2B86
2887
2B88
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
220
216
227
216
235
236
220
222
226
214
230
213
217
208
230
225
226
213
228
205
225
245
213
228
205
225
245
215
233
222
216
230
217
233
210
223
223
215
214
234
237
202
218
215
223
227
274
269
283
285
300
294
289
263
280
265
291
268
283
265
293
283
284
293
259
309
290
288
277
293
269
285
311
277
268
273
278
296
276
294
270
288
280
286
275
300
305
266
276
275
287
289
311
316
317
336
343
334
332
295
325
297
327
299
322
308
333
326
333
336
294
370
337
335
318
328
307
327
354
326
336
311
325
340
321
342
307
333
331
330
321
344
349
323
313
310
340
325
318
320
338
344
365
344
345
305
331
307
340
310
334
310
346
350
348
355
305
385
348
351
333
344
322
339
369
338
350
317
357
319
329
338
353
354
350
350
332
361
363
339
331
320
355
343
350
363
387
392
410
376
388
348
374
352
378
346
346
353
384
391
391
400
340
439
388
394
374
387
364
371
412
383
397
353
404
360
372
379
401
387
386
397
369
390
400
381
358
346
404
384
364
384
408
412
426
395
412
357
392
366
396
363
382
373
402
413
4 09
418
356
463
407
410
388
402
390
396
433
404
413
367
424
377
390
409
419
411
410
426
392
418
418
409
378
366
425
404
391
394
441
443
456
425
449
396
426
398
437
382
422
399
435
446
451
452
391
495
448
442
422
433
429
434
482
445
441
392
458
418
423
441
451
449
450
469
420
456
448
458
410
397
452
439
D-3
-------
SU6CHRONIC TOXICITt OF ORTHO-CRESOL [N SPRAGUE DAWLEY RATS
MALE BODY WEIGHT DATA Cg)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE
50 rng/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
219
210
215
210
209
223
245
223
219
226
226
235
230
232
203
214
228
235
219
236
220
215
229
221
212
229
220
224
194
229
235
210
215
212
216
209
217
225
203
225
226
215
214
225
273
271
274
263
262
237
316
2S4
276
293
290
3Q2
295
297
243
267
282
236
273
303
279
273
280
276
264
285
258
275
231
282
287
252
252
256
264
260
272
284
- 242
284
285
266
254
276
298
318
320
316
300
350
367
326
309
327
328
351
345
346
287
312
331
340
325
368
329
329
324
324
311
339
290
303
275
333
362
304
305
301
315
312
332
336
281
346
339
313
301
313
313
329
339
318
317
360
389
341
322
341
345
375
359
363
291
323
342
359
333
384
349
342
343
343
327
362
299
336
290
338
384
318
320
311
322
324
344
355
248
373
359
332
322
320
341
371 .
384
369
348
412
432
384
372
375
382
428
406
411
328
379
386
404
374
419
395
383
385
397
372
404
333
390
343
380
428
358
363
348
359
372
389
408
326
411
386
366
364
354
360
394
402
382
375
443
458
402
391
398
411
449
424
423
249
402
415
425
385
445
426
403
407
421
392
432
351
413
368
398
453
383
388
368
387
393
411
439
348
434.
427
383
383
373
385
430
438
417
410
443
493
428
422
431
446
474
459
460
375
431
447
460
416
483
476
441
442
470
423
469
374
448
410
430
492
419
425
392
415
422
444
482
375
474
470
416
396
397
D-4
-------
SUBCHRON1C TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAHLEY RATS
MALE BODY WEIGHT DATA (g)
ANIMAL NO. WEEK 1 WEEK 2 UEEIC 3 UEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL;
600 mg/kg/day
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
214
226
211
227
218
226
216
216
224
216
244
240
215
224
219
220
220
218
215
213
222
231
227
224
218
219
218
231
217
215
245
280
258
270
270
267
248
239
263
246
291
291
dead
272
260
262
253
256
254
264
250
279
272
266
dead
26G
270
275
261
260
277
301
302
308
295
301
285
296
300
283
344
335
dead
dead
312
294
293
290
308
290
291
323
325
312
dead
309
313
314
dead
298
286-
308
319
316
dead
316
290
310
306
294
350
341
dead
dead
323
306
286
293
315
300
305
335
330
328
dead
316
325
318
dead
300
332
343
362
347
dead
350
317
344
341
325
394
370
dead
dead
366
341
322
dead
357
338
335
375
372
369
dead
358
343
353
dead
301
356
347
378
361
dead
367
329
359
258
322
418
383
dead
dead
383
356
336
dead
379
351
349
389
389
386
dead
373
363
370
dead
330
382
359
399
386
dead
407
362
394
384
334
445
413
dead
dead
410
dead
360
dead
416
375
380
385
428
423
dead
408
377
401
dead
360
D-5
-------
SU8CHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
KALE BODY WEIGHT DATA (g)
DOSE LEVEL
ANIMAL NO. 'WEEK 8 UEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK 14
0 mg/kg/day _- 2881
-" 2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
29130
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
416
418
453
463
477
439
471
414
434
410
453
396
443
417
459
466
485
474
425
515
451
463
450
462
452
455
502
458
461
413
408
434
352
380
371
472
462
482
426
474
469
470
442
408
474
466
na
na
na
na
na
na
na
na
na
na
476
416
460
442
474
498
502
496
441
554
485
482
467
477
471
473
531
480
478
417
na
na
na
na
na
na
na
na
na
na
486
503
448
434
496
479
na
na
na
na
na
na
na
na
na
na
496
430
475
455
490
508
511
521
456
574
507
504
477
488
485
489
552
500
492
445
na
na
na
na
na
na
na
na
na
na
500
532
472
448
516
494
na
na
na
na
na
na
na
na
na
na
469
412
471
465
501
489
506
513
464
576
479
494
474
507
490
461
534
507
494
463
na
na
na
na
na
na
na
na
na
na
478
529
473
449
521
473
na
na
na
na
na
na
na
na
ne
na
502
447
502
472
514
526
544
544
479
609
505
525
504
533
518
503
549
493
472
473
na
na
na
na
na
na
na
na
na
na
512
537
505
466
545
510
na
na
na
na
na
na
na
na
na
na
526
451
521
491
523
543
559
563
492
627
540
552
523
549
533
524
575
527
501
489
na
na
na
na
na
na
na
na
na
na
525
531
532
481
557
539
na .
na
n3
na
na
na
na
na
na
na
548
463
533
502
533
558
569
578
502
648
562
567
538
564
549
542
601
559
518
499
na
na
na
na
na
na
na
na
na
na
538
602
543
498
576
553
na = no data available.
D-6
-------
SUBCHRONIC TOXICITY Of CRTHD-CRESOL IN SPRAGU6 OAULEY RATS
MALE SOOT WEIGHT DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK 14
DOSE LEVEL
50 mg/kg/day 2930
• (continued) .-" 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
405
463
462
446
433
513
527
455
442
444
472
494
481
496
375
457
48Q
492
439
497
501
449
443
496
442
506
400
477
435
450
507
445
452
410
435
447
478
506
395
504
500
440
423
413
418
436
475
466
450
543
541
477
462
468
488
515
504
520
na
na
na
na
na
na
na
na
na
na
465
520
422
504
464
472
523
462
471
425
450
469
510
542
418
522
525
454
455
431
429
504
504
480
426
558
558
493
477
478
514
542
520
541
na
na
na
na
na
na
na
na
na
na
496
543
425
516
498
489
554
478
492
444
469
499
518
568
467
551
547
424
475
446
423
497
510
503
422
546
559
499
487
451
505
553
529
556
na
na
na
na
na
na
na
na
na
na
513
572
444
543
526
512
585
502
517
465
482
524
545
589
459
577
588
476
485
457
445
520
.533
521
466
591
582
524
511
496
543
574
545
574
na
na
na
na
na
na
na
na
na
na
530
587
463
558
553
521
621
522
542
488
502
542
572
614
481
602
597
503
480
475
455
541
558
539
460
601
602
536
512
511
555
594
561
595
na
na
na
na
na
na
na
na
na
na
548
614
478
582
570
534
629
523
555
501
513
554
592
627
493
624
611
516
490
481
467
557
567
554
472
621
619
547
524
510
581
613
581
609
na
na
na
na
na
na
na
na
na
na
557
616
501
605
578
549
651
545
567
514
522
569
603
650
503
627
631
527
507
492
na = no data available.
D-7
-------
SUBCHRON1C TOXICITY Of ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
MALE 3QOY WEIGHT DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 UEEK 11 WEEK 12 WEEK 13 WEEK 14
DOSE LEVEL
600 mg/kg/day 2980
r 2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2994
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
403
380
403
407
dead
406
376
404
412
334
466
437
dead
dead
436
dead
379
dead
433
393
385
391
440
436
dead
412
393
419
dead
388
na
na
na
na
dead
na
na
na
na
na
490
464
dead
dead
469
dead
393
dead
459
402
412
422
470
440
dead
427
dead
432
dead
373
na
na
na
na
dead
na
na
na
na
na
508
478
dead
dead
495
dead
404
dead
474
410
429
448
472
474
dead
409
dead
335
dead
393
na
na
na
na
dead
na
na
na
na
na
527
493
dead
dead
515
dead
421
dead
485
415
dead
368
498
493
dead
442
dead
415
dead
412
na
na
na
na
dead
na
na
na
na
na
546
512
dead
dead
544
dead
439
dead
503
430
dead
426
525
512
dead
469
dead
455
dead
435
na
na
na
na
dead
na
na
na
na
na
561
520
dead
dead -
558
dead
447
dead
511
441
dead
449
543
525
dead
488
dead
487
dead
446
na
na
na
na
dead
na
na
na
na
na
566
531
dead
dead
581
dead
453
dead
524
453
dead
481
557
541
dead
511
dead
517
dead
456
na = no data available.
D-a
-------
SU8CHROMSC TOXICITY OF ORTHO-CRESOL IN SP8AGUE DAULEY RATS
' MALE BODY WEIGHT CAIN DATA Cg)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 MEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
0 mg/kg/day
50 ng/kg/day
2881
2882
2883
2884
2885
2886
288?
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
54
53
56
69
65
58
69
41
54
51
61
55
66
57
63
58
58
80
31
104
65
43
64
65
64
60
66
62
35
51
62
66
59
61
60
65
57
71
61
66
68
64
58
60
64
62
91
100
90
120
108
93
112
73
99
83
97
86
105
100
103
101
107
123
66
165
112
90
105
100
102
102
109
111
103
89
109
110
104
109
97
110
108
115
107
110,
112
121
95
95
117
98
98
104
111
128
130
ioa
125
83
105
93
110
97
117
102
116
125
122
142
77
180
123
106
120
116
117
114
124
123
117
95
141
89
112
105
143
131
127
135
118
127
126
137
113
105
132
116
130
147
160
176
175
140
168
126
148
138
148
133
129
145
154
166
165
187
112
234
163
149
161
159
159
146
167
163
164
131
188
130
155
146
191
164
163
182
155
156
163
179
140
131
18T
157
144
168
181
196
191
159
192
135
166
152
166
150
165
165
172
188
183
205
128
258
182
165
175
174
185
171
188
189
180
145
208
147
173
176
209
188
187
211
178
184
181
207
160
151
202
177
171
178
214
227
221
189
229
174
200
184
207
169
205
191
205
221
225
239
163
290
223
197
209
205
224
209
237
230
208
170
242
188
206
208
241
226
227
254
206
222
211
256
192
182
229
212
196
202
226
247
242
203
251
192
208
196
223
183
226
209
229
241
259
261
197
310
226
218
237
234
247
230
257
243
228
191
192
204
135
147
161
249
239
267
212
240
232
268
224
193
251
239
D-9
-------
SUBCHRON1C TOX1C1TY OF ORTHO-CRESOL IN SPRAGUE OAULEY RATS
' MALE SOOY WEIGHT GAIN DATA (g)
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
50 mg/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/diy 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
54
61
59
53
53
9
71
61
57
67
64
67
65
65
35
53
54
51
54
67
59
58
51
55
52
56
38
51
37
53
52
42
37
44
48
51
55
59
39
59
59
51
40
51
79
108
105
106
91
122
122
103
90
101
102
116
115
114
79
98
103
105
106
132
109
114
95
103
99
110
70
79
81
104
127
94
90
89
99
103
115
111
78
121
113
98
87
88
94
119
124
108
108
132
144
118
103
115
119
140
129
131
83
114
114
124
114
148
129
127
114
122
115
133
79
112
96
109
149
108
105
99
106
115
127
130
45
148
133
117
108
95
122
161
169
159
139
184
187
161
153
149
156
193
176
179
120
165
158
169
155
183
175
168
156
176
160
175
113
166
149
151
193
148
148
136
143
163
172
183
123
186
160
151
150
129
141
184
187
172
166
215
213
179
172
172
185
214
194
196
41
188
187
190
166
209
206
193
178
200
180
203
131
189
174
169
218
173
173
156
171
184
194
214
145
209
201
168
169
148
166
220
223
207
201
215
248
205
203
205
220
239
229
228
167
217
219
225
197
247
256
226
213
249
211
240
154
224
216
201
257
209
210
180
199
213
227
257
172
249
244
201
182
172
186
253
247
236
224
285
282
232
223
218
246
259
251
264
167
243
252
257
220
261
281
234
214
275
230
277
180
253
241
221
272
235
237
198
219
233
261
281
192
279
274
225
209
188
D-10
-------
SUSCHRQNIC TQXICI1Y OF ORTHO-CRESOL IN SPRAGUE DAHL6Y RATS
' MALE BOOT WEIGHT GAIN DATA
-------
SUSCHRONIC TOX1C1TY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
'MALE BODY WEIGHT GAIN DATA eg)
ANIMAL HO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
0 mg/kg/diy 2381
2882
2883
2384
2885
2886
2887
2888
28B9
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
na
ne
na
na
na
na
na
na
na
na
246
203
243
234
244
273
276
283
213
349
260
237
254
249
266
248
286
265
245
195
na
na
na
na
na
na
na
na
na
na
249
301
230
219
273
252
na
na
na
na
na
na
na
na
na
na
266
217
258
247
260
283
285
308
228
369
232
259
264
260
230
264
307
285,
259
223
na
na
na
na
na
na
na
na
na
na
263
330
254
233
293
267
na
na
na
na
na
na
na
na
na
na
239
199
254
257
271
264
280
300
236
371
254
249
261
279
285
236
289
292
261
241
na
na
na
na
na
na
na
na
na
na
241
327
255
234
298
246
na
na
na
na
na
na
na
na
na
na
272
234
285
264
284
301
318
331
251
404
280
280
291
305
313
273
304
278
239
251
na
na
na
na
na
na
na
na
na
na
275
335
287
251
322
283
na
na
na
na
na
na
na
na
na
na
296
238
304
283
293
318
333
350
264
422
315
307
310
321
328
299
330
312
268
267
na
na
na
na
na
na
na
na
na
na
288
379
314
266
334
312
na
na
na
na
na
na
na
na
na
na
318
250
316
294
303
333
343
365
274
443
337
322
325
336
344
317
356
344
285
277
na
na
na
na
na
na
na
na
na
na
301
400
325
283
353
326
na = no data available.
D-12
-------
SUBCHRONIC TOXICITt OF QRTHO-CRESOl IN SPRAGUE OAUIEY RATS
'NALE BODY UEIGHT GAIN DATA
-------
SUBCHRONIC TOXICITT OF ORTHQ-CRESOL IN SPRAGUE DAWLEY RATS
' MALE BODY UEIGHT GAIN DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 UEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
600 mg/kg/day 2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
.3005
3006
3007
3008
3009
ns
na
na
na
na
na
na
na
na
na
246
224
na
na
250
na
173
na
244
1B9
190
191
243
236
na
208
na
201
na
158
na
na
na
na
na
na
na
na
na
na
264
238
na
na
276
na
184
na
259
197
207
217
245
250
na
190
na
104
na
178
na
na
na
na
na
na
na
na
na
na
283
253
na
na
296
na
201
na
270
202
na
137
271
269
na
223
na
184
na
197
.na
na
na
na
na
na
na
na
na
na
302
272
na
na
325
na
219
na
283
217
na
195
298
283
na
250
na
224
na
220
na
na
na
na
na
na
na
na
na
na
317
280
na
na
339
na
227
na
296
228
na
218
316
301
na
269
na
256
na
231
na
na
na
na
na
na
na
na
na
na
322
291
na
na
362
na
233
na
309
239
na
250
330
317
na
292
na
ZB6
na
241
na = no data available,
D-14
-------
SUBCHRONIC icxicm OF ORTHQ-CRESOI IN SPRAGUE DAULEY RATS
FEMALE BODf WEIGHT DATA (g)
DOSE LEVEL.
0 mg/kg/day
ANIMAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 UEEK 7
50 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
30Z5
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
161
156
144
163
170
171
155
150
164
153
164
147
165
152
158
155
157
164
154
155
153
153
153
155
162
138
142
153
141
156
158
162
147
164
161
160
157
149
152
167
151
163
176
161
151
159
178
177
166
188
200
190
176
168
188
171
177
171
181
175
190
169
177
185
176
175
166
171
170
171
182
151
163
169
165
177
178
184
172
188
139
177
179
173
163
192
166
196
202
177
166
177
204
198
183
213
229
215
198
191
207
189
202
197
218
191
216
196
199
204
188
192
184
188
190
194
195
177
208
190
187
196
194
209
192
206
211
193
205
188
178
215
185
214
237
197
182
203
202
200
182
217
238
215
202
200
202
198
208
198
222
197
219
199
205
208
196
189
195
195
193
188
202
203
178
208
194
186
198
209
200
212
220
194
207
194
184
220
189
224
238
197
184
207
230
220
197
242
260
231
215
203
223
211
230
217
244
214
232
222
224
228
215
212
208
210
208
214
224
203
222
222
204
213
222
226
220
233
240
216
228
215
198
250
203
234
262
223
204
227
235
230
201
241
268
225
227
215
229
212
224
221
246
203
246
217
227
225
217
210
207
214
208
220
222
205
221
218
210
212
225
236
232
240
248
217
229
218
201
249
210
247
264
224
205
237
249
242
212
260
280
256 .
242
230
243
221
237
238
268
218
258
234
249
238
232
227
221
230
222
236
227
239
23Q
230
230
223
235
249
245
243
251
233
244
234
211
263
222
262
282
238
220
254
D-15
-------
SUBCHRQNIC TOXICITY OF ORTHO-CRESOL JN SPRftGUE DAULEr RATS
FEMALE iOOY WEIGHT DATA (g)
AMIMAL NO. UEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 UEEK 6 UEEK 7
50 mgAg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 ing/ kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
169
157
153
162
156
166
145
153
160
166
154
156
149
156
163
149
183
150
159
155
148
149
147
157
155
162
145
158
151
153
na
160
141
150
167
170
158
166
155
156
170
161
149
167
183
180
174
190
179
183
164
178
184
194
180
174
173
184
186
174
212
166
183
171
174
164
166
183
172
176
171
185
177
177
166
188
161
169
189
202
178
189
158
182
193
183
168
198
216
202
195
216
202
215
183
204
206
217
202
198
189
205
209
203
241
188
211
193
193
184
181
209
195
193
191
209
197
199
181
207
183
193
207
229
194
208
189
205
225
207
179
217
213
210
196
221
208
220
189
217
217
218
211
199
194
212
215
204
248
189
208
204
190
186
186
207
199
198
193
214
203
206
182
22D
1B4
193
209
232
203
210
196
207
231
213
176
220
230
229
216
243
221
241
204
244
236
245
224
218
213
238
234
224
272
210
227
216
208
206
198
226
226
210
200
234
226
232
198
223
200
213
220
262
229
237
207
224
254
230
' 159
232
244
236
223
252
223
251
206
255
248
255
235
223
218
na
237
235
281
215
232
224
211
211
207
237
232
214
216
245
234
231
200
231
207
216
235
265
238
242
208
233
255
237
190
247
267
254
236
276
246
266
215
266
255
272
246
230
236
264
246
248
292
224
252
236
229
228
214
240
244
216
225
259
248
250
212
236
216
224
245
282
252
251
224
257
262
263
210
256
na = no data available; body weights inadvertently
not recorded,
D-16
-------
SUBCHRONIC TCXIC1TY OF ORTHO-CRESOl IN SPRAGUE DAWLEY RATS
FEMALE BODY WEIGHT DATA Cg)
ANIMAL MO. UE£K 1 WEEK 2 WEEK 3 WEEK 4 WEhK 5 WEEK 6 WEEK 7
DOSE LEVEt
600 mg/kg/day
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
161
127
143
161
145
170
141
152
157
155
156
154
161
160
152
156
160
158
155
138
156
146
138
158
146
163
162
166
138
177
174
151
169
132
160
190
159
177
173
dead
172
169
179
170
170
dead
181
180
162
154
179
159
158
176
163
183
173
186
148
202
193
168
195
201
185
214
176
198
197
dead
194
190
201
184
199
.dead
194
206
190
172
192
dead
179
191
181
dead
dead
208
166
224
dead
176
199
207
189
220
176
201
198
dead
196
188
203
, 186
200
dead
198
209
189
dead
dead
dead
dead
198
185
dead
dead
211
171
222
dead
185
209
216
202
242
193
209
207
dead
dead
dead
226
201
216
dead
210
244
208
dead
dead
dead
dead
209
201
dead
dead
232
dead
255
dead
196
222
232
208
227
204
214
215
dead
dead
dead
224
209
218
dead
211
255
218
dead
dead
dead
dead
215
208
dead
dead
231
dead
258
dead
dead
230
235
222
259
212
215
220
dead
dead
dead
dead
dead
dead
dead
224
256
226
dead
dead
dead
dead
216
219
dead
dead
240
dead
dead
D-17
-------
SUBCHRQNIC TOXtClTY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE BCOY WEIGHT DATA (g)
ANIMAL HO. WEEK a WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK 14
DOSE LEVEL
0 mg/kg/day 3013.
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
- 3039
3040
3041
3042
50 mg/kg/day 3044
3047
3068
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
253
252
219
262
283
263
248
236
242
213
238
241
272
226
267
241
242
241
237
234
235
239
227
235
240
236
242
237
239
232
237
256
247
263
272
229
2S7
241
217
265
232
273
292
247
222
260
na
na
na
na
na
na
na
na
na
na
245
250
294
234
285
252
262
247
246
242
242
243
240
245
246
246
261
245
247
236
na
na
na
na
na
na
na
na
na
na
243
290
302
264
224
275
na
na
na
na
na
na
na
na
na
na
254
256
298
238
296
253
262
252
255
248
247
240
239
247
254
259
257
247
252
241
na
na
na
na
na
na
na
na
na
na
249
297
307
271
232
283
na
na
na
na
na
na
na
na
na
na
253
E58
305
245
294
263
267
256
265
259
259
250
254
249
260
263
267
264
266
249
na
na
na
na
na
na
na
na
na
na
257
307 '
332
278
239'
287
na
na
na
na
na
na
na
na
na
na
257
267
315
247
310
272
274
263
275
269
258
253
262
254
254
266
271
264
268
241
na
na
na
na
na
na
na
na
na
na
262
315
338
236
246
297
na
na
na
na
na
na
na
na
na
na
255
271
318
251
310
276
269
263
274
273
267
260
257
260
256
273
276
268
263
246
na
na
na
na
na
na
na
na
na
na
266
323
345
284
244
304
na
na
na
na
na
na
na
na
na
na
260
275
320
255
310
279
282
265
274
273
269
266
255
263
266
282
277
275
273
253
na
na
na
na
na
na
na
na
na
na
275
335
347
289
253
309
na = no data available.
0-18
-------
SUBCHRONIC TQXiCiTY OF ORTHO-CRESOL IK SPRAGUE DAWLEY RATS
FEMALE SCOT WEIGHT DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK t4
DOSE LEVEL
50 mg/kg/day 3062-
(continued) 3063
3064
3065
3066
3067
3063
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3068
3089
309C
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
271
260
245
287
253
278
223
266
269
277
250
236
243
268
249
260
286
226
257
245
238
225
216
248
250
225
231
267
248
255
222
242
227
229
254
292
263
259
230
248
275
208
204
264
290
268
255
297
269
286
232
283
288
289
263
245
259
280
na
na
na
na
na
na
na
na
na
na
261
235
243
275
268
267
227
254
236
240
263
301
268
270
238
259
285
259
217
278
290
274
255
307
272
291
238
305
288
290
268
248
266
292
na
na
na
na
na
na
na
na
na
na
265
241
247
292
269
276
227
260
239
246
274
311
275
275
242
275
299
267
214
281
301
275
264
322
281
304
241
307
293
297
281
260
273
297
na
na
na
na
na
na
na
na
na
na
264
233
248
288
280
277
226
261
253
245
279
309
281
278
248
286
299
269
229
289
318
290
265
333
285
312
244
323
302
305
289
266
281
303
na
na
na
na
na
na
na
na
na
na
274
241
262
302
295
292
239
262
241
245
291
322
290
2S3
263
300
303
281
231
294
313
239
269
339
287
312
249
328
308
309
283
247
280
321
na
na
na
na
na
na
na
na
na
na
276
244
264
309
304
304
247
270
260
251
299
315
290
287
267
302
313
289
234
294
321
289
274
345
291
326
254
336
315
315
293
265
294
325
na
na
na
na
na
na
na
na
na
na
282
252
263
312
303
303
258
275
259
260
304
324
295
289
269
317
311
288
238
294
na = no data available.
0-19
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE BODY WEIGHT DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13 WEEK 14
DOSE LEVEL
600 mg/kg/day 3112
31 IT
31H
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
dead
dead
228
236
218
260
207
226
223
dead
dead
dead
dead
dead
dead
dead
224
264
229
dead
dead
died
dead
229
219
dead
dead
249
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
2Z4
272
236
dead
dead
dead
dead
215
225
dead
dead
260
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
234
281
240
dead
dead
dead
dead
233
236
deed
dead
263
dead ,
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
240
287
247
dead
dead
dead -
dead
242
247
dead
dead
271
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
243
296
259
dead
dead
dead
dead
245
254
dead
dead
275
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
257
303
258
dead
dead
dead
dead
247
270
dead
dead
285
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
265
306
256
dead
dead
dead
dead
255
275
dead
dead
284
dead
dead
na = no data available.
D-20
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRACUE DAWIEY RATS
' FEMALE BODY WEIGHT GAIN DATA (g)
ANIMAL NO. WEEK 1 UEEK 2 WEEK 3 WEEK 4 WEEK 5 WEESC 6 WEEK 7
DOSE LEVEL:
0 mg/kg/day 3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
303Z
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
50 mg/kg/day 3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
17
21
22
25
30
19
21
18
24
18
13
24
16
23
32
14
20
2T
22
20
13
18
17
16
20
13
21
16
24
21
20
22
25
24
28
17
22
24
11
25
15
33
26
16
15
18
43
42
39
50
59
44
43
41
43
36
38
50
53
39
58
41
42
40
34
37
31
35
37
39
33
39
66
37
46
40
36
47
45
42
50
33
48
39
26
48
34
51
61
36
31
44
41
44
38
54
68
44
47
50
38
45
44
51
57
45
61
44
48
44
42
34
42
42
40
33
40
65
36
55
53
30
40
47
53
48
59
34
50
45
32
53
38
61
62
36
33
48
69
64
S3
79
90
60
60
53
59
58
66
70
79
62
74
67
67
64
61
57
55
57
55
59
62
65
80
69
63
57
64
64
73
69
79
56
71
66
46
83
52
71
86
62
53
68
74
74
57
78
98
54
72
65
65
59
60
74
81
56
88
62
70
61
63
55
54
61
55
65
60
67
79
65
69
56
67
74
85
76
87
57
72
69
49
82
59
84
88
63
54
78
88
86
68
97
110
85
87
80
79
68
73
91
103
66
100
79
92
74
78
72
68
77
69
81
65
101
88
77
89
67
77
87
98
84
90
73
87
85
59
96
71
99
106
77
69
95
92
96
75
99
113
92
93
36
78
60
74
94
107
74
109
86
85
77
83
79
82
86
74
80
78
98
100
84
98
76
79
94
100
99
111
69
100
92
65
98
81
110
116
86
71
101
D-21
-------
SUBCHRONIC TOXICITY CF QRTHQ-CRESQl IN SPRAGUE DAWIEY RATS
' FEMALE BODY WEIGHT GAIN DATA Cg)
AN[HAL NO. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 WEEK 6 WEEK 7
DOSE LEVEL
50 ing/kg/day 3062
{continued} 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/ kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097.
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
14
23
21
28
23
17
19
25
24
23
26
18
24
28
23
25
29
16
24
16
26
15
19
26
17
14
26
27
26
24
na
28
20
19
22
32
20
23
3
26
23
22
19
31
47
45
42
54
46
49
38
51
46
51
48
42
40
49
46
54
58
38
52
38
45
35
34
52
40
31
46
51
46
46
na
47
42
43
40
59
36
42
34
49
55
46
30
50
49
53
43
59
52
54
44
64
57
52
57
43
45
56
52
55
65
39
49
49
42
37
39
50
44
36
48
56
57
53
na
60
43
43
42
62
45
44
41
51
61
52
27
53
61
72
63
81
65
75
59
91
76
79
70
62
64
82
71
75
89
60
68
61
60
57
51
69
71
48
55
76
75
79
na
63
59
63
53
92
71
71
52
68
64
69
10
65
75
79
70
90
72
85
61
102
88
89
81
67
69
na
74
86
98
65
73
69
70
62
60
80
77
52
71
87
83
78
na
71
66
66
68
95
80
76
53
77
85
76
41
80
98
97
83
114
90
100
70
113
95
106
92
74
87
108
83
99
109
74
93
81
81
79
67
83
89
54
80
101
97
97
na
76
75
74
78
112
94
85
69
101
92
102
61
89
102
103
92
125
97
112
78
113
109
111
96
80
94
112
86
111
103
76
98
90
90
76
69
91
95
63
86
109
97
102
ne
82
86
79
87
122
105
93
75
92
105
47
55
97
na = no data available.
D-22
-------
SUBCHRONIC TOXICITT OF QRTHO-CRESQl IN SPRAGUE DAWLET RATS
" FEMALE BODY WEIGHT GASH DATA (g)
AMI HAL NO. WEEIC 1 WEEK 2 WEEK 3 WEEK 4 UEEK 5 WEEK 6 WEEK 7
600 mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
31Z3
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
13
H4
26
21
15
20
18
25
16
na
16
15
18
10
18
na
21
22
7
16
23
13
20
18
17
20
11
20
10
25
32
41
52
40
40
44
35
46
40
na
38
36
40
24
47
na
34
48
35
34
36
na
41
33
35
na
na
42
28
47
na
49
56
46
44
50
35
49
41
na
40
34
42
26
48
na
38
51
34
na
na
na
na
40
39
na
na
45
33
45
na
58
66
55
57
72
52
57
50
na
na
na
65
41
64
na
50
66
53
na
na
na
na
51
55
na
na
66
na
78
na
69
79
71
63
57
63
62
58
na
na
na
63
49
66
na
51
97
63
na
na
na
na
57
62
na
na
65
na
81
na
na
87
74
77
89
71
63
63
na
na
na
na
na
na
na
64
98
71
na
na
na
na
58
73
na
na
74
na
na
na
na
85
75
73
90
66
74
66
na
na
na
na
na
na
na
64
106
74
na
na
na
na
71
73
na
na
83
na
na
na = no data available.
D-23
-------
SU8CHRCNIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE BODY WEIGHT CAIN DATA
-------
SU3CHROKIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWLcY RATS
FEMALE BOOY WEIGHT GAIN DATA
-------
SUBCHROMIC TOXICITY CF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE BODY yElGHT GAIN DATA (g)
ANIMAL NO. WEEK 8 WEEK 9 WEEK 10 WEEK 11 WEEK 12 WEEK 13
DOSE LEVEL
600 mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
64
114
81
na
na
na
na
57
79
na
na
94
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
74
123
85
na
na
na
na
75
90
na
na
97
na
na
na
na
na
na
na
na
na
na>
na
na
na
na
na
na
na
na
80
129
92
na
na
na
na
84
101
na
na
105
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
83
138
104
na
na
na
na
87
108
na
na
109
na
na
na
na
na
na
na
na
na
na
. na
na
na
na
na
na
na
na
97
145
103
na
na
na
na
89
124
na
na
119
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
105
148
101
na
na
na
na
97
129
na
na
118
na
na
na = no data available.
D-26
-------
SUBCHROHIC TOXIC1TY OF ORTHO-CRESOL Itt SPRAGUE 0AWLEY RATS
KALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NO. week 1 week 2 week 3 week 4 week 5 week 6 week 7
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
2831
2B82
2883
2384
2685
2886
2387
2B88
2889
2890
2891
2892
2893
2394
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
23.1
22.7
22.1
26.8
25.5
26.2
22.7
20.4
22.4
22.3
24.5
21.4
23.4
21.4
24.3
22.9
22.7
26.8
21.0
28.2
25.1
25.5
21,3
24.9
22.5
24.7
26.8
23.9
22.9
23.5
25.0
25.0
22.3
25.9
22.0
23.0
23.2
23.1
22.6
27.6
23.6
21.3
21.3
22.1
22.8
24.7
33.8
17.7
24.7
30.0
28.2
27.7
26.2
22.8
26.7
23,1
26.3
22.9
25. 9
24.7
27.4
26.7
26.4
16.2
23.5
33.8
28.6
27.3
24.6
26. 8
25.3
28. 5
30.4
26.3
26.4
15.0
25.8
26.6
26.1
29.5
24.0
26.1
28.0
26.5
26.8
31.8
27.9
27.9
24.6
25.0
26.5
27.2
22.2
22.9
24.4
2S.2
25.6
28.3
25.3
20.0
24.8
22.5
24.9
20.5
24.5
21.0
23.8
24.9
25.2
33.6
23.9
34.0
25.4
27.1
22.5
28.6
25.0
27.3
31.0
23.6
18.4
22.4
14.0
22.7
22.3
25.5
25.0
26.0
24.6
26.3
23.8
30.7
24.2
26.6
22.7
21.5
25.3
26.7
16.0
23.9
26.1
28.2
29.8
25.4
25.2
23.5
25.7
23.0
25.3
21.5
20 .B
22.3
24.3
24.7
26.8
28.5
23.1
29.7
25.6
25.9
24.1
25.8
28.0
25.5
30.2
24.4
25.8
25.3
27.0
22.6
22.4
26.6
27.1
23.4
22.3
27.5
25.1
25.1
22.4
25.8
22.3
21.4
25.3
23,9
21.9
23.5
24.7
27.3
25.9
25.9
24.6
22.6
24.8
22.1
25.2
20.3
23.5
21.7
23.3
25.3
26.1
27.7
23.6
31.2
25.2
27.2
24.5
25.3
26.3
27.0
31.7
24.5
24.5
23.4
25.5
23.4
22.8
28.3
27.3
23.7
24.1
27.7
24,4
28.8
23.0
27.3
22.3
20.8
23.8
24.7
22.9
18.8
'24.0
26.6
27.1
26.3
24.7
22.9
26.0
21.4
26.3
2D.6
31.4
22.3
24.2
25.8
28.7
30.1
28.1
33.0
24.2
27.7
E3.6
28.0
25.6
24.7
31.9
28.8
25.3
22.8
21.1
23.3
14.8
16.8
16.1
24.5
23.5
27.4
22.6
26.6
23.8
26.6
25.2
21.3
24.0
25.7
38.7
22.2
18.5
20,3
22.0
18.0
30.2
8.9
17.0
16.8
24.5
17.1
21.1
19.5
22.0
21.1
22.0
25.0
24.3
26.9
21.8
25.5
21.6
25.3
22.8
23.4
28.8
22.1
21.9
23.1
6.6
17.5
3.5
3.9
3.5
17.3
19.9
21.6
16.0
26.4
20.1
23.3
22.1
20.2
20.5
26.5
D-27
-------
SUBCHRONtC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAUIEY RATS
MALE FOOD CONSUMPTION DATA (g/day3
ANIMAL NO, week 1 week 2 week 3 heek 4 wsek 5 week 6 week 7
DOSE LEVEL
50 mg/kg/day 2930
(continued) 293f
• 2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
22.6
21.5
21.6
23.5
20,9
25.2
24.4
23.2
24.5
23.1
22,8
25.5
26.0
24.2
18.4
21.5
27.5
22.3
22.5
27.6
22.3
25.6
23.0
21.9
20.5
24.1
21.1
20.8
17.6
22.8
27.9
19.1
22.0
22.3
23.8
21.3
24.6
26.8
21.0
23.7
24.8
19.9
24.5
16.2
23.6
22.8
28.9
26.9
24.6
30.6
29.7
27.1
26.0
25.2
26.7
28.4
30.6
29.3
22.0
26.1
26.3
25.7
24.3
30.9
25.5
25.5
24.6
24.5
24.1
27,6
37.9
22.6
20.8
25.1
27.7
26.8
24.5
24.0
25.3
24.6
26.8
26.0
23.4
28.3
27.2
24.3
24.8
23.3
22.9
24.6
25.9
25.8
22.5
27.5
26.2
25.2
25.3
22.6
22.5
27.3
29.2
26.6
20.6
23.2
25.8
24.7
20.5
28.4
24.9
23.6
22.0
22.0
23.4
28.5
19.8
23.8
20.9
22.6
27.9
22.7
25.4
23.4
22.5
23.5
23.2
26,0
18.2
23.1
26.7
21.8
21.8
19.7
20.7
24.5
25.3
26.0
21.5
27.2
26.0
24.8
27.5
20.9
22.0
28.1
29.6
26,7
21.5
24.5
27.8
26.1
22.9
28.3
29.8
28.2
26.6
29.0
26.5
28.2
22.2
27.8
24.3
24.1
30.3
23.3
27.2
25.0
23.4
25.0
27.8
29.7
22.3
27.2
29.8
25.6
29.8
25.3
21.0
25.3
24.5
24.8
23.4
25.6
24.9
21.5
25. Z
21.5
23.0
25.2
23.4
25.5
22.6
23.9
28.8
24.0
20.8
28.3
28.5
23.6
24.9
28.0
22.3
26.7
21.7
26.6
24.1
23.6
29.6
22.0
25.0
24.2
23.3
23.1
25.3
30.4
22.9
26.1
29.2
21.3
17.1
21.8
21.1
26.6
24.0
'26.1
22.7
29.4
27.0
22.8
24.0
19.2
24.4
24.2
29.1
26.1
21.8
25.0
29.6
27.3
23.4
27.1
28.8
25.6
26.1
30.5
22.1
27.3
23.3
25.8
24.3
24.5
26.5
23.3
27.4
24.2
25.9
24.4
27.9
30.5
24.5
27.6
32.5
21.1
23.1
20.1
17.8
23.9
21.9
23.2
17.2
25.6
24.7
21.6
23.1
20.1
20,2
23.6
25.2
24.0
14.5
18.3
25.7
20.3
20.8
33.0
29.5
19.2
22.3
23.3
20.8
24.1
21.8
25.7
24.8
23.3
23.7
20.8
28.9
22.9
19.8
21.4
25,1
30.6
22,4
24.1
28.4
21.9
23.8
21.5
D-28
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE OAWLEY RATS
HALE FCX)D CONSUMPTION DATA (9/day)
ANIMAL MO. week 1 week 2 yeek 3 week 4 week 5 week 6 week 7
DOSE LEVEL
600 mg/kg/day 2980
2981
29S2
29S3
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009 •
17.4
24.3
19.7
22.3
23.3
22,1
18.3
18.8
20.2
19.7
24.7
24.1
na
23.0
21.2
20.6
21.9
20.1
18.9
26.3
12.0
20.8
21.7
22.1
na
20.0
21.7
21.9
.21.1
'21.4
19.1
19.7
24.2
22.4
22.2
22.0
19.3
21.4
23.4
21.3
26.4
26.5
na
na
25.4
24.2
23.0
22.7
24.6
19.7
21.3
23.3
26.4
24.0
na
26.4
23.6
24.3
3.6
22.2
18.1
24.3
24.3
21.4
na
25.6
17.8
21.0
19.7
21.5
25.3
22.2
na
na
22.4
19.0
18.3
na
22.4
18.1
20.2
22.2
24.4
25.1
na
24.1
20.6
21.6
na
20.9
23.8
24.3
26.1
23.6
na
25,6
20.0
23,0
24.0
23.9
26.6
26.8-
na
na
19.1
25.8
22,6
na
24.4
22.1
23.2
20.8
26.2
25.8
na
20.8
19.5
23.3
na
16.8
21.2
Z1.5
20.6
21.8
na
26.4
20.S
22.5
24.4
19,0
26.2
23 .a
na
na
25.1
22.8
21.8
na
23.4
20.2
20.8
21.8
27.4
26.9
na
25.5
21.8
24.3
na
20.1
21.3
19.4
,21.2
23.6
na
23.6
20.7
22.0
23.1
17.6
25.5
24.6
na
na
26.0
na
22.3
na
23.1
19.8
21.0
17.7
28,0
23.0
na
23.2
19.5
21.7
rva
21.0
17.9
18.4
16.3
19.3
na
16.7
15.2
22.8
18.4
19.7
23.2
21.8
na
na
25.6
na
18.7
na
El. 7
18.3
17.9
16.4
22.3
22.4
na
21.0
21.0
21.6
na
18.4
na = no data available.
D-29
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAQUE DAUIEY RATS
HALE FOOD CONSUMPTION DATA Cg/day)
ANIMAL NO. week B week 9 week 10 week 11 week 12 week 13
DOSE LEVEL
0 mg/kg/day -' 2881
2882
2883
2884
2885
2886
2SS7
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
na
na
na
na
na
na
na
na
na
na
22.9
16.2
20.2
18.4
20.2
Z0.2
23.5
26.0
22.5
28.9
21.6
25.0
18.9
23.3
20.3
22.3
27.8
22.2
20.7
19.7
na
na
na
na
na
na
na
na
na
na
16.9
24.8
19.4
20.0
20.4
18.3
na
na
na
na
na
08
na
na
na
na
10.8
11.7
14.0
16.6
19.5
10.6
11.8
17.7
17.5
21.8
11.0
16.9
13.3
18.7
19.1
10.7
17.1
17.9
18.2
21.2
na
na
na
na
na
na
na
na
na
na
12.7
16.2
15.1
15.2
19.2
10.5
na
na
na
na
na
na
na
na
na
na
22.5
20.0
21.3
18.3
20.9
20.5
25.0
24.4
22.9
29.0
22.0
25.5
23.3
24.6
21.3
22.8
21.7
12.3
11.2
23.6
na
na
na
na
na
na
na
na
na
na
17.9
20.7
23.6
19.3
19.8
21.8
na
na
na
na
na
na
na
na
na
na
26.1
17.8
21.1
21.4
21.2
23.8
24.8
25.0
22.7
29.4
24.0
26.4
22.5
23,4
21.1
26.2
25.5
24.5
22.1
20.7
na
na
na
na
na
na
na
na
na
na
23.6
22.7
22.9
20.4
22.1
25.8
na
na
na
na
na
na
na
na
na
na
25.9
18.7
21.6
20.3
19.3
23.2
22.5
23.7
21.9
29.3
23.8
26.0
21.3
23.1
21.0
25.3
26.8
24.9
22.0
22.6
na
na
na
na
na
na
na
na
na
na
19.1
26.4
23.1
20.2
21.6
23.!
na
na
na
na
na
na
na
na
na
na
25.4
16.5
20.5
19.5
19.7
21.6
22.7
22.3
18.2
26.2
23.5
25.6
21.6
23.5
19.4
27.6
22.6
24.8
20.7
20.9
na
na
na
na
na
na
na
na
na
na
17.6
24.7
21.2
19.9
7.0
22.2
na = no data available.
0-30
-------
SUBCKRQNJC TOX1CITY OF QRTHO-CRESOL IN SPSAGUE DAWLEY RATS
HALE FOCO CONSUMPTION DATA (g/day)
ANIMAL NO. week 3 week 9 week 10 week 11 week 12 week 13
DOSE LEVEL
50 mg/ kg/day . 2930'
(continued} / 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
H954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
16.6
23.1
20.3
22.4
15.3
24.7
24.4
21.6
20.6
15.3
19.2
24.0
24.3
23.5
na
na
na
na
na
na
na
na
na
na
21.4
24.7
18.1
24.1
23.3
20.7
27.0
20.3
23.5
23.3
20.1
22.5
26.0
26.1
21.0
25.0
27.6
10.9
20.9
20.1
12.4
15.9
18.4
21.3
4.0
.a
16.5
16.9
17.7
9.1
12.3
18.4
21.0
24.1
na
na
na
na
na
na
na
na
na
na
20.5
24.6
21.1
25.9
24.6
22.5
28.8
22.4
24.1
24.7
20.5
22.6
24.4
28.3
21.3
25.5
31.3
19.4
35.2
19.7
19.7
22.0
22.0
23.0
19.2
25.2
24.5
21.7
20.3
19.2
21.1
23.4
24,8
23.9
na
na
na
na
na
na
na
ne
na
na
21.9
24.7
20.4
23.0
24.5
22.0
23.5
20.1
24.5
22.4
19.8
22.3
25.4
26.6
20.9
26.1
28.7
21.2
15.7
19.0
19.3
23.3
25.5
25.4
19.9
26.8
24.2
21.7
19.3
20.8
21.9
25.2
26.1
23.9
na
na
na
na
na
na
na
na
na
na
22.2
24.0
21.6
24.6
27.1
21.0
29.5
20.3
23.7
24.6
21.4
21.9
26.9
27.3
22.4
27.5
27.9
20.9
18.5
19.4
18.5
22.7
21.9
23.7
15.4
24.5
9.9
20.9
19.5
19.6
20. B
22.9
25.8
23.7
na
na
na
na
na
na
na
na
na
na
20.5
23.5
21.7
25.1
17.7
21.5
28.8
19.2
23.9
23.8
22.3
22.5
26.8
27.8
22.0
26.7
27.5
20.3
19.3
18.8
16.7
23.0
23.5
24.6
17.4
24.5
24.4
20.0
21.3
16.1
19.3
22.9
25.5
23.8
na
na
na
ra
na
na
na
na
na
na
21.0
19.5
23.7
24.2
25.8
22.6
28.6
20.2
23.9
23.5
20.6
20.8
8.5
26.1
22.0
25.4
25.3
21.5
20.7
16.7
a Value not valid
na = no data available.
D-31
-------
SUBCHRONIC TOX1C1TY OF ORTHO-CRESDL IN SPWGUE DAHLEY RATS
HALE FOOD CONSUMPTION DATA Cg/day}
ANIMAL NO. yeek 8 week 9 week 10 ye«k 11 week 12 week 13
DOSE LEVEL
600 mg/kg/day 2980
/ 2981
2982
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3QQ7
3008
3009
na
na
na
na
na
na
na
na
na
na
25.0
22.4
na
na
27,0
na
19.0
na
21.4
16.0
20.1
19.5
25.5
21.2
ni
11.3
na
9.8
na
15.2
na
na
na
na
na
na
na
na
na
na
23.0
22.4
na
na
26.0
na
19.7
na
26.3
16.6
20.7
9.2
23.8
24.6
na
25.7
na
13.9
na
18.1
na
na
na
na
na
na
na
na
na
na
23.1
21.6
na
na
27.9
na
19.8
na
23.2
17.2
4.8
16.4
2B.Q
23.1
na
24.3
na
26.5
na
20,0
na
na
na
na
na
na
na
na
na
na
24.1
22,1
na
na
28.5
na
19.4
na
21.9
18.2
na
22.7
28. Q
23.5
na
21.9
na
28.4
na
20.5
na
na
na
na
na
na
na
na
na
na
23.1
23.6
na
na
28.9
na
21.0
na
22.6
18.7
na
21. a
27.1
24.3
na
24.4
na
28.4
na
20.1
na
na
na
na
na
na
na
na
na
na
21.3
22.1
na
na
27.3
na
19.5
na
22.3
14.7
na
21.8 '
25.8
21.9
na
23.3
na
28.3
na
19.9
na = no data available.
D-32
-------
SUBCHRQMIC TOXICITY OF ORTHO-CRESOL IN SPRACUE DAWLEY RATS
HALE 1=000 CONSUMPTION DATA (g)
IFeeder Weights]
ANIMAL NO, new 1 old 1 new 2 old 2 new 3 old 3
DOSE LEVEL
0 mg/kg/day
50 ing/kg/day
28S1
2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
292?
292B
2929
452
466
422
435
455
448
447
435
451
432
416
449
447
440
453
462
457
452
464
459
450
432
46a
426
450
415
439
432
441
418
422
388
445
428
435
458
428
424
457
443
448
453
438
449
457
438
290.2
307.4
267.1
247.2
276,2
264.5
288.2
291.9
294.5
272.2
244.6
299.4
283.3
290.4
283.2
301.4
298.4
264,3
316.9
261.9
274.6
253.2
318.6
251.5
292.5
242.1
251.6
264.4
280.6
253.5
246.7
212.8
288.7
246.9
280.9
296.8
265.9
262.0
298.8
249.9
283.0
303.6
288.9
294.6
297.5
264.9
600.6
543.8
551.3
579.6
561.5
600.4
579.6
559.2
574.9
614.4
576.2
565.4
620.0
605.1
565.0
560,6
588.1
577.0
5S8.5
578.2
619.4
594.9
598.6
608.9
627.3
577.8
556.1
579.9
568.8
579.7
538.3
585.9
613.0
554.3
587.5
579.4
594.1
599.4
620.2
621.0
590.2
582.3
575.1
590.2
590.3
571.4
364.1
419.8
378.6
369.8
364.4
406.3
396.5
399.3
388.0
452.6
391.8
405.1
439.0
432.0
373.5
374.0
403.2
463.6
424.2
341.5
419.4
404.1
426.1
421.1
450.0
378.0
343.4
395.8
383.8
474.8
357.7
400.0
430.2
347.8
419.6
396.4
398.0
413.7
432.4
398.6
395.1
386.9
402.6
415.2
405.0
381.0
541.3
504.9
502.1
531.1
529.4
544.0
545.8
513.6
526.6
538.5
505.1
501.3
542.8
463.1
484.1
476.5
521.3
521.4
466.9
453.6
527.8
495.7
513.0
522.1
518.1
450.1
486.2
474.8
466.2
505.8
478.8
505.6
471.7
502.7
497.0
491.5
477.2
487.8
463.3
454.5
448,8
467.1
483.2
494.9
472.8
505.1
385.7
344.9
331.6
333.8
349.9
346.1
369.0
373.4
353.2
380.7
330.7
357.5
371.3
315,9
317.7
302.5
345.2
286.5
299.9
215.9
349.9
305.8
355.2
322.2
343.1
258.9
269.2
309.7
337.5
348.7
381.0
346.9
315.9'
324.2
321.7
309.5
305.3
303.6
296.9
239.3
279.5
281.0
329.0
344.4
295.9
318. 1
D-33
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IK SPRAGUE DAUIEY RATS
KALi FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 1 old 1 new 2 old 2 new 3 old 3
DOSE LEVEL--
50 mg/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
449
464
423
412
432
451
415
447
453
481
472
427
416
442
529
459
412
443
439
430
446
443
430
412
452
419
428
406
438
429
395
427
422
407
417
476
423
423
432
451
408
475
422
416
290.6
313.6
272.0
247.2
286.0
274.6
244.4
284.4
231.6
319.3
312.3
248.7
233.7
272.4
400.3
308.2
219.7
286.8
281.4
237.1
290.0
263.5
268.8
258.9
308.5
250.1
280.0
260.7
315.0
269.3
199.8
293.2
26S.O
250.6
250.3
326.6
250.9
240.3
285.3
285.4
234.5
335.6
250.8
302.8
603.1
569.8
590.5
602.4
578.3
596.0
624.0
620.6
607.2
712.0
582.7
600.6
566.5
619.9
737.6
569.1
608.1
603.0
615.4
579.3
592.1
590.8
570.4
594.2
658.8
581.2
597.2
577.0
178.9
571.3
607.8
566.8
537.4
551.4
576.8
605.3
581.3
569.0
570.2
609.7
607.3
608.5
593.1
591.7
403,1
430.5
383,3
413.8
406.2
381.5
415.9'
430.6
425.3
535.3
395.8
402.1
352.3
414.5
583.3
386-3
420.3
422.8
445.4
363.1
413.7
412.6
398.1
422.9
490.4
388.3
331.7
419.0
433.3
395.8
414.2
379.0
366.0
383.5
399.8
432.9
393.4
387.1
406.1
407.8
416.8
438.7
419.3
428.5
465.8
477.1
462.9
470.8
483.6
477.0
505.4
486.8
470.4
535.3
504.6
496.6
477,7
502.2
583.3
488.0
483.8
4S2.2
505.5
485.2
485.0
514.2
510,6
518.0
558.5
479.5
484.9
482.9
510.2
512.7
507.7
460.0
488.4
469.4
481.3
510.0
473.7
490.9
504.0
472.3
502.6
438.7
518.3
533.6
305.3
304.6
231.8
290.0
325.9
284.6
322.3
310.6
293.0
377,1
347.4
305.3
273,0
316.0
439.3
325.4
303.0
309.5
362.1
286.1
310.8
348.8
356.6
364.3
394.8
279.7
346.2
316.1
364.2
354.7
312.5
301.0
310.9
305.6
323.9
345.8
311.4
308.9
376.6
310.5
315.7
285.9
365.4
395.7
D-34
-------
SU8CHRGNIC TOXICtTY OF Q8THQ-CRESQL IN SPRAGUE DAWLSY RATS
HALE FOOD CONSUMPTION DATA
-------
SUBCHRQN1C TOXICITY OF ORTKO-CRESOL IN SPRAGUE DAWLEY RATS
HALE FOOD CONSUMPTION DATA
-------
SUBCHROMIC TOXICITY OF ORTHQ-CRESOL IN SPRAGUE DAyLEV RATS
HALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANiHAL NO. new 4 old 4 new 5 old 5 new 6 old 6
DOSE LEVEL
50 mg/ kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
461.
1
454.6
433.
452.
439.
435.
414.
439.
413.
544.
438.
438.
439.
417,
475.
410.
407.
409.
8
0
7
4
5
4
9
5
8
6
9
8
2
4
6
2
452.4
436.
483.
464.
458.
463.
465.
457.
448.
411.
456.
421.
469.
433.
423.
482.
454.
435.
440.
422.
420.
437.
440.
453.
462.
432,
6
7
5
3
2
2
1
3
8
8
8
5
3
4
6
5
9
2
2
\
2
4
7
3
1
316.
282.
256.
Z69.
288.
244.
232.
266.
221.
398.
284.
241.
233.
231.
325.
238.
212.
226.
291.
233.
275,
267.
272.
259.
279.
259.
292.
217.
286.
253.
257.
270.
233.
307.
290.
261.
245.
214.
263.
246.
231.
274.
253.
254.
2
8
5
7
9
8
8
1
7
2
7
8
0
2
0
8
9
8
8
3
3
1
0
9
5
5
7
2
7
1
4
0
3
6
a
0
6
4
8
8
8
2
6
8
461
451
438
4S4
492
446
473
438
477
550
491
460
463
511
592
501
457
486
505
518
499
492
492
478
563
500
531
431
480
500
483
476
491
516
526
496
506
473
518
537
499
516
526
480
.5
.1
.2
.6
.1
.8
.7
.3
.3
.3
.2
.9
.0
.1
.7
.8
.7
.3
.8
.1
.0
.2
.2
.1
.5
.2
.0
.5
.6
.7
.0
.4
.5
.9
.6
.9
.7
.7
.1
.1
.9
.6
.0
.8
314.
274.
266.
311.
328.
267.
299.
287.
300.
399.
330.
234.
264.
332.
434.
334.
256.
318.
360.
320.
299.
327.
317.
282.
407.
313.
378.
245.
311.
335.
275.
322.
316.
347.
363.
335.
329.
261.
357,
354.
295.
367.
406.
323.
6
3
6
1
1
7
1
8
9
9
5
4
2
9
6
7
2
2
0
1
7
1
9
3
7
2
9
6
7
8
5
2
5
5
4
4
9
0
7
6
4
7
6
5
498
507
496
495
507
505
505
480
496
488
486
492
470
525
519
505
476
498
498
489
506
469
470
494
520
482
474
474
508
478
482
484
471
508
516
499
479
479
499
473
471
489
483
465
.8
.9
.1
.6
.5
.5
.7
.0
.6"
.7
.6
.7
.9
.8
.9
.5
.6
.8
.6
.5
.0
.9
.0
.4
.6
.8
.0
.3
.0
.4
.2
.8
.5
.9
.7
.5
.7
.8
.4
.3
.5
.7
.3
.6
350.9
321.4
327.9
312.9
348.9
299.4
316.5
320.7
328.6
354.0
315.6
323.5
267.0
342.8
367.3
330.3
269.1
307.4
335.1
299.5
304.1
290.4
287.3
280.8
365.9
291.5
310.6
293.7
337.9
306.7
297.0
321.5
279.7
339.3
335.7
328.7
2S4.6
266.3
328.2
280.2
244.3
341.8
321.8
325.2
D-37
-------
SUBCHRQNIC TOXICITY OF ORTHO-CRESOL IH SPRAGUE DAWLEY RATS
MALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO, new 4 old 4 new 5 old 5 new 6 old 6
DOSE LEVEL.
600 mg/icg/day 2980
Z981
2932
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
479.1
463.6
447.6
430.8
na
401.9
440.2
461.8
452.8
451.5
415.2
503.8
na
na
461.0
457.6
432.4
na
447.7
420.9
435.4
413.7
441.0
430.4
na
432.8
455.7
429.1
na
430.8
312.3
293.2
264.7
265.7
na
222.9
299.9
300.5
285.0
284.5
229.3
315.9
na
na
327.5
276.8
274.2
na
277.0
266.5
272.8
267.9
257.3
250.1
na
287.1
319.2
266.3
na
313.3
535.1
501.0
483.2
467.2
na
500.7
521.6
503.3
470.4
498.7
484.6
470.7
na
na
489.2
479.8
497.2
na
497.2
478.0
481.2
500.4
481.6
483.3
na
474.2
496.8
442.6
na
452.4
386.7
350.6
344.3
314.4
na
315.6
378.3
345.7
299.7
365.6
300.9
304.3
na
na
313.7
319.9
344.9
na
333.7
336.5
335.5
347.6
289.5
294.9
na
295.5
344.4
272.4
na
311.8
481.6
499.8
472.5
471.0
na
464.9
495.7
501.7
461.0
507.1
445.4
484.0
na
na
437.2
na
493.6
na
488.0
489.0
479.4
486.4
451.2
464.7
na
489.1
478.5
486.0
na
475.6
332.2
364.3
324.1
306,1
na
299.8
350.9
347.4
299.5
384.2
266.7
311.8
na
na
305.5
na
337.2
na
326.1
350.2
332.5
362.8
255.4
303.4
na
326.4
342.0
334.0
na
328.3
na = no data available.
D-38
-------
SUBCHRONIC TOXICm OF ORTHO-CRESOL IN SPRACUE PAWIEY RATS
MALE FOOD CONSUMPTION DATA (g)
[Feeder Ueightsl
ANIMAL NO. new 7 old 7 new 8 old 8 new 9 old 9
DOSE LEVEL
0 mg/kg/day 2831
2882
2883
2884
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
416
344
361
344
379
326
357
325
331
331
491
498
494
476
480
483
474
490
493
493
473
491
494
475
478
485
475
490
465
490
349
411
358
356
377
348
336
348
329
320
486
475
472
496
474
477
.2
.6
.9
.5
.6
,8
.6
.1
.8
.9
.4
.8
.3
.9
.7
.7
.7
.7
,1
.5
.7
.8
.3
.4
.0
.3
.9
.1
.7
.4
.8
.5
.3
.3
.6
.2
.9
.5
.5
,5
.5
.7
.9
,9
.1
.9
300
300
324
283
313
290
267
298
297
281
319
379
,1
,3
.9
.7
.7
.8
.1
.4
.9
.4
.8
.1
346.5
340
327
336
320
315
322
305
321
313
342
298
318
321
274
335
312
329
330
359
347
348
367
296
297
283
297
267
346
312
318
355
330
292
.1
.0
.0
.8
.5
.9
.0
.2
.2
.8
.6
.7
.4
.5
.5
.6
.0
.0
,1
.9
.5
.2
.3
.1
.8
.5
.8
.0
,9
.0
.3
.6
.1
421
na
na
na
na
na
na
na
na
na
na
.7
.426.6
425
415
420
.7
.4
.0
427.3
413
425
435
423
427
426
474
437
423
421
421
419
422
419
428
426
438
430
431
441
.4
.0
.0
.7
.1
.6
.3
.2
.4
.5
.1
.0
.6
.4
na
na
na
na
na
na
na
na
na
na
.0
,9
.8
.0
.9
.3
na
na
na
na
na
na
na
na
na
na
261.2
313.3
284.2
286.9
278.5
286.2
249.1
242.9
277.4
221.5
275.6
251.5
342.3
274.0
281.6
265.3
226.2
263.3
277.4
281.7
na
na
na
na
na
na
na
na
na
na
309.9
253.1
302.9
289.9
289.0
313.5
418
429
419
443
381
434
391
424
431
446
433
443
472
454
438
445
422
423
418
421
398
380
404
432
436
437
na
na
na
na
na
na
na
na
na
na
.3
.3
.3
.6
.9
.1
.5
.2
.8
.6
.7
.4
.5
.1
.8
.1
.5
.9
.9
.8
na
na
na
na
na
na
na
na
na
na
.4
.0
.2
.6
,9
.9
342
na
na
na
na
na
na
na
na
na
na
.8
347.4
321
.3
327.2
245
359
308
300
309
293
356
325
379
322
304
370
302
298
291
273
309
266
298
326
302
364
.6
.9
.8
.2
.1
.7
.9
.3
.2
.9
.8
,2
.7
.5
.2
.4
na
na
na
na
na
na
na
na
na
na
.6
,9
.6
.2
.6
.7
na = no data available.
D-39
-------
SUBCHROMIC TOXICITY OF QRTHQ-CRESOL IN SPRAGUE DAUIEY RATS
HALE FOOD CONSUMPTION CATA (3)
[Feeder Weights]
ANIMAL NO. new 7 old 7 new 8 old 8 new 9 old 9
DOSE LEVEL
50 rag/ kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
484.2
487.4
489.0
456.4
472.5
452.0
478,5
465.3
485.4
430. 2
486.6
452.9
452.0
447,9
367.3
351.4
421.4
381.9
358.9
395.0
349.9
338.8
509.1
345.3
523.6
451.1
469.9
468.8
487.1
485.8
456.6
436.3
470.8
468.0
468.0
481.9
492.9
544.7
465.9
474.5
453.8
493.4
475.3
483.4
359.6
319.9
335.9
294.3
351.9
272.7
305.9
314.0
323.8
339.2
345.2
288.0
275.3
279.6
338.4
296.4
344.3
320.9
296.6
329.0
290.9
300.5
464.5
298.6
377.8
282.3
317.2
289.1
313.5
322.9
290.6
340.9
268.2
307.4
329.1
331.8
317.2
330.3
308.9
306.1
255.3
339.8
308.9
333.0
437.9
433.3
423.1
426.4
424.4
416.4
416.9
425.4
421.5
432.3
424.5
425.4
427.2
429.4
na
na
na
na
na
na
na
na
na
na
443.9
423.7
415.9
421.9
415.4
425.9
424.5
422.7
425.3
418.8
419.6
421.1
429.4
445.0
428.2
426.9
425.9
438.9
417.4
415.5 .
321.8
276.7
277.2
269.3
317.3
243.7
246.3
274.5
277.3
325.0
2S9.9
257.6
253.6
264.8
na
na
na
na
na
na
na
na
na
na
294.0
250.5
289.2
253.1
252.1
2B1.2
235.7
280.7
260.9
255.8
278.6
263.5
247.2
262.4
281.2
252.2
232.4
362.8
271.4
274.5
426.1
440.8
437.3
430.9
451.7
382.6
418.4
449.7
505.3
506.7
458.5
460.9
497.5
431.5
na
na
na
na
na
na
na
na
na
na
426.2
419.1
457.3
437.3
442.5
439.2
415.9
425.7
435.5
411.9
450.2
436.8
434.5
428.5
431.0
478.7
463.0
438.4
493.6
433.9
339.5
329.2
308.4
281.8
423.6
475.7
302.6
331.5
381,4
443.2
372.2
332.1
350.6
262.5
na
na
na
na
na
na
na
na
na
na
282.7
246.7
309.5
255.8
270.5
282.0
214.1
268.9
266.8
238.7
306.9
278.7
263.5
230.7
281.8
300.3
243.8
302.8
247.2
296.3
na = no data available.
D-40
-------
SUBCHRONIC TOX1C1TY OF ORTHO-CRESOL IN SPRAGUS DAULEY RATS
MALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 7 old 7 new 8 old 8 new 9 old 9
DOSE LEVEL,
600 mg/k9/day 2980
2981
2982
2983
2984
29S5
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
449.2
502.4
357.7
363.4
na
355.0
350.9
347.4
350.9
334.2
475.8
466.3
na
na
449.6
na
494.1
na
475.5
466.9
454.9
470.8
445.5
442.4
na
455.7
456.1
435.5
na
470.8
395.4
447,2
325.2
305.5
na
321.6
305.3
301.8
295.7
344.8
313.1
313.6
na
na
Z70.6
na
363.3
na
323.7
338.9
329.6
355.9
289.7
285.5
na
308. 6
393.2
254.6
na
341.9
na
na
na
na
na
na
na
na
na
na
426.6
431.5
na
na
422.9
na
424.5
na
422.4
430.2
421.2
422.1
418.9
420.6
na
426.9
na
423.6
na
417.4
na
na
na
na
na
na
na
na
na
na
251.6
274.9
na
na
234,2
na
291.5
na
272.3
318.5
280.8
285.3
240.7
272.3
na
348.0
na
355.2
na
310.9
na
na
na
na
na
na
na
na
na
na
485.8
490.9
na
na
432.6
na
446.1
na
438.9
433.5
492.6
465.1
463.8
458.8
na
434.3
na
453.8
na
445.2
na
na
na
na
na
na
na
na
na
na
325.1
333.9
na
na
250.7
na
308.1
na
254,6
317.5
347.5
401.0
297.0
286.3
na
254.2
na
356.4
na
318.3
na = no data available.
D-41
-------
SU3CHRONIC TOXIC!TY OF OSTHO-CRESOL IN SPRAGUE DAUtEY RATS
HALE FOOD CONSUMPTION DATA (g)
[Fesdsr Weights]
ANiMAL NO. new 10 old 10 new 11 old 11 ney 12 old 12 new 13 old 13
DOSE LEVEL
0 mg/kg/day 2881
2882
2883
2884
2885
2886
2887
28S8
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
50 mg/kg/day 2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
na
Hi
na
na
na
na
na
na
na
na
425.0
423.2
425,4
424.8
405.4
424.3
423.7
423.8
418.3
422.9
421.5
424.0
472.0
420.0
426.9
424,1
402.4
420.5
428.0
424.6
na
na
na
na
na
na
na
na
na
na
433.2
431.4
437.5
425.3
430.6
432.6
na
na
na
na
na
na
na
na
na
na
267.3
282.9
2?6.0
297.0
259.2
280.5
248.7
252.8
257.7
219.8
267.5
245.5
308.6
247.6
278.1
264.3
250.5
334.3
349.8
259.6
na
na
na
na
na
na
na
na
na
na
307.9
286.8
272.6
290.4
291.8
280.2
na
na
na
na
na
na
na
na
na
na
425.7
425.9
426.5
429.8
427.0
426.2
427.2
427.2
428.2
430.7
429.2
431.4
429.7
426.3
426.4
429.3
426.9
429.2
429.1
427.5
na
na
na
na
. na
na
na
na
na
na
434.3
438.0
432.3
436.2
434.1
442.2
na
na
na
na
na
na
na
na
na
na
243.3
301.6
278.6
280.1
278.5
259,3
253.8
252.3
269.0
225.2
261.0
246.9
272.3
262.4
278.6
246.1
248.7
257.4
274.2
282.4
na
na
na
na
na
na
na
na
na
na
269.1
278.8
272.3
293.5
279.5
261.6
na
na
na
na
na
na
na
na
na
na
455.4
465.5
455.4
455.3
466.2
459.3
464.6
458.3
464.4
448.2
466.0
458.1
457.7
484.6
456.1
454.1
453.4
453.2
450.4
438.8
na
na
na
na
na
na
na
na
na
na
436,6
449.7
452.1
451.5
445.6
442.0
na
na
na
na.
na
na
na
na
na
na
273.8
334.5
304.0
313,0
331.3
297.1
307.3
292.7
311.3
243.4
299.5
276.3
308.7
323.1
309.1
276.7
266.1
278.9
296.7
280.8
na
na
na
na
na
na
na
na
na
na
303.0
264.6
290.5
309,8
294.6
280.1
na
na
na
na
na
na
na
na
na
na
463.8
466.8
429.8
443.9
470.1
463.1
465.2
447.2
436.3
457.7
470.7
466.7
458.1
468.3
480.1
485.3
443.7
443.5
461.3
426.5
na
na
na
na
na
na
na
na
na
na
447.5
489.2
451.4
457.6
444.3
423.9
na
na
na
na
na
na
na
na
na
na
311.6
36S.1
307.0
307.1
332.3
333.3
329.1
291.0
308.6
300.3
306.4
313.2
307.0
327.1
344.4
319.6
285.7
270,2
316.4
280.5
na
• na
na
na
na
na
na
na
na
na
324.2
316.6
302.7
318.3
395.0
290.9
na = no data available.
D-42
-------
SUBCKRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAVJLEY RATS
HALE FOOD CONSUMPTION DATA
-------
SUBCHRONIC TOXIC!TY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
MALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 10 old 10 new 11 old 11 new 12 old 12 new 13 old 13
DOSE LEVEL
600 mg/kg/day 2980
2981
29S2
2983
2984
2985
2986
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
na
na
na
na
na
na
na
na
na
na
420.0
422,9
na
na
424.1
na
420.6
na
444.6
423.6
434.7
423.0
436.0
445.1
na
422.5
na
431.0
na
427.2
na
na
na
na
na
na
na
na
na
na
258.4
271.4
na
na
228.6
na
282.1
na
282.4
302.9
401.2
307.9
239.7
283.6
na
252.2
na
245,8
na
287.0
na
na
na
na
na
na
na
na
na
na
438,4
426.7
na
na
430.5
na
427,2
na
437.6
430.6
na
426.3
424.3
439.3
na
425.7
na
434.8
na
429.4
na
na
na
na
na
na
na
na
na
na
269,9
271,7
na
na
231.0
na
291.3
na
234,2
303.4
na
267.5
228.2
274.8
na
272.1
na
235.9
na
285.6
na
na
na
na
na
na
na
na
na
na
455.1
449.2
na
na
442.7
na
442.9
na
445.1
468.7
na
441.9
444.4
467.6
na
478.2
na
432.2
na
462.5
na
na
na
na
na
na
na
na
na
na
293.4
283.7
na
na
240.4
na
296.2
na
286.7
337.7
na
289.3
254.7
297.2
na
307.1
na
233.4
na
322.1
na
na
na
na
na
na
na
na
na
na
518.3
554.6
na
na
506,2
na
533.2
na
500.7
517.8
na
463.7
517.3
536.1
na
518.5
na
502. 9
na
505.0
na
na
na
na
na
na
na
na
na
na
390.5
422.1
na
na
315.3
na
416.0
na
366.8
414.8
na
311.2
337.0
404.6
na
355.7
na
304.8
na
366.0
na = no data available.
D-44
-------
SUBCHRQN1C TOXICITY OF ORTHO-CRESOL IN SPRAGUE OAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NO. week 1 week 2 week 3 week 4 week 5 week 6 week 7
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3013
30 H
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
30Z8
3029
3030
3031
' 3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
14.8
17.2
14.6
17.0
18.5
16.1
15.8
15.5
18.4
13.5
14.5
13.8
ia.3
16.1
18.0
15.0
15.1
15.6
14.3
16.8
13.9
13.4
13.3
14.3
17.4
13.2
15.5
13.9
14.8
16.6
15.1
13.3
14.9
16.0
15.8
14.3
14.7
12.8
12.7
16.1
0.7
17.2
15.7
15,1
14.8
13.3
17.2
16.1
14.3
23.5
20.8
13.6
17,7
18.6
18.6
15.8
18.5
2.5
21.6
12.0
35.5
19.8
16.9
17.0
8.7
.24.7
16.8
12.2
17.9
13.9
14.2
23.1
14.9
11.1
0.6
31.0
16.1
14.4
16.0
17.6
17.7
16.1
22.4
7.8
14.8
18. 2
16.8
18.0
19.4
16.2
15.5
16.6
26.3
15.6
14.1
18.9
23.3
17.2
16.8
16.4
13.9
14.4
17.2
14.8
44.1
15.0
10.2
24.1
16.3
15.6
15.0
17.2
15,4
19.8
13.9
22.6
17.3
14.5
13.2
18.5
27.4
14.3
14.8
14.1
16.3
14.8
17.1
14.2
9.4
20.1
12.6
17.1
14.3
16.4
18.8
15.3
15.2
15.7
1,7.9
16.6
13.5
23.7
22.3
16.3
16.2
15.9
15.8
16.0
15.6
13.9
24.3
16.5
18.7
16.6
16.7
14.8
15.0
18.0
15.5
14.9
14.9
14.9
19.4
15.8
15.7
17.8
14.0
14.8
14.5
14.4
15.3
15.7
15.8
15.0
16.6
14.0
13.3
26.0
13.8
15,4
18.7
14.5
14.4
15.3
17.1 '
20.1
14,8
'18.4
19.9
16.4
16.8
16.0
15.4
13.3
16.7
13.9
28.5
13.7
19.4
15.4
17.0
14,0
14.8
18.0
13.6
15.5
14.3
14.3
17.8
16.1
17.9
16.6
14.7
13.9
14.0
14.7
17.1
30.2
15.8
14.9
15.1
13.6
13.8
16.4
14.1
17.2
17.2
15.4
14.4
16.9
15.5
15.6
14.9
20.5
21.7
15.0
15.3
17.1
14.6
13.9
15.6
14.8
27.0
28.2
19.2
16.3
17.9
13.8,
16.0
17.6
15.1
15,1
14.5
13.3
17.0
16.4
16.4
17.6
15.3
14.7
13.8
14.7
17.0
13.8
15.9
11.9
15.6
13.7
15.3
20.1
15.3
16.4
18.1
16.0
15.8
15.7
13.4
11.9
10. 1
15.7
13.0
16.5
14.4
14.2
13.7
9.3
13.9
13.1
22,1
13.3
17.5
13.4
12.9
12.2
13,1
14.7
14.5
13,4
13.3
12.0
16.3
13.2
15.1
13.7
13.1
13.0
27.3
1.7
14.1
32.1
.a
23.9
7.0
3.8
5,3
15.5
13.5
15.9
13.7
14.4
14.0
13.8
aValue not valid
D-45
-------
SUBCHRON-IC TOXICITY OF ORTHO-CRESOl IN SPRAGUE DAWLElf RATS
FEMALE FOOD CONSUMPTION DATA (S/day)
ANIMAL NO. yeek 1 week 2 week 3 week 4 week 5 week 6 week 7
DOSE LEVEL
50 i^/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
13.9
14.7
14.5
18.0
15.7
15.8
11,7
13.9
13.7
17.9
15.5
14.0
16.2
15.6
15.4
15.4
15.6
13.9
14.6
15.3
14.7
17.1
13.7
16.4
17.4
13.8
17.3
15.9
16.2
14.8
15.0
17.0
14.0
14.9
14.4
18.6
13.3
17.1
21,4
17.4
16.8
16.1
16.2
19.6
17.7
11.5
21.9
14.8
24,9
18.7
14.6
16,5
12.7
22.1
18.0
16.3
23.2
12,7
17.9
17.9
21.9
14.1
15.3
15.3
14.5
13.0
14.8
6.3
11.2
Z3.4
11.8
18.2
21.2
6.3
16.6
17.3
14.3
15.6
15.3
18.0
15.3
16.4
16.9 •
10.1
18.3
16.5
15.0
17.8
21.1
16.4
17.6
17.8
19,1
18.1
14.9
16,6
15.7
20.3
16.4
15.4
17.2
16.9
12.7
19.6
22.7
14.4
14.5
12.3
12.5
12.6
13.0
26.3
18.4
4.8
21.4
16.1
14.9
25.4
5,6
19.7
13.8
13.1
14.6
16.4
14,1
15.7
13.4
32.4
15.4
5.2
22.8
15.2
14.7
15.7
15.1
19.4
14.7
20.8
13.8
16.8
26.0
18.0
15.4
15.9
18.8
17.4
18.9
17,0
22.2
15.2
16.6
15.5
13.6
13.0
13.5
15.3
18.0
12.2
15.8
15.4
19.5
15.6
15.7
14.4
14,3
14.3
14.5
18.7
15.4
17.8
14.3
30.2
17,4
16.0
9.4
16.5
17.1
15.7 "
15.9
19.6
15.8
17.8
12.6
16.8
16.4
17.1
15.1
13.9
18.3
17.4
16.2
15.4
20.9
13.5
17.3
15,5
13.5
12.7
12.8
15.3
16.5
12.8
16.4
17.4
21.3
15.7
15.7
15.0
14.5
15,0
16.2
17.5
14.7
15.7
13.1
25.3
16.0
14.4
15.6
17.9
16.4
16.5
16.3
20.2
16.2
17.2
13.2
17.8
17,6
18.5
16.0
14.3
20.3
18.7
14.3
15.2
18.7
14.8
16.7
17.1
14.7
15.1
14.2
14.4
17,3
13.1
16.7
18.2
15.5
16.1
14.9
14.2
14.7
15.2
15.7
18,3
14.2
16.8
14,3
23.0
17.7
9.7
14.2
18.3
15.3
14.7
15-7
17.4
15.2
17.4
12.5
16.3
15.8
14.0
14.7
12.9
15.8
16.5
15.7
11.0
19.6
11.0
11.0
13.6
.a
14.2
22.6
14.1
12.3
11.9
13.9
15.4
13.6
12.8
14.8
12.3
12.8
13.6
13.2
16.1
11.9
14.5
13.5
13.9
13.7
11.9
11.0
15.5
not valid
0-46
-------
SUBCHRONIC TOXICITY OF CRTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA Cg/day)
ANIMAL NO. week 1 week 2 week 3 week 4 week 5 week 6 week 7
DOSE LEVEL
600 ms/ kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
11.9
12,6
15.3
15.5
14.2
15.8
12.8
14.3
13.9
rva
13.9
12.3
13.4
11.4
13.7
na
15.0
15.9
9.7
13.4
12.6
12.2
11.5
13.2
15.5
14.9
12.5
14.8
12.0
19.8
14.7
13.8
15.5
16.9
15.1
16.7
13.0
18. 1
15.5
na
15.6
13.3
14.1
13.1
15.0
na
14.0
17.7
14.1
14.2
14.2
14.7
9.9
13.5
18.0
7.2
0.2
16.5
13.4
18.6
na
10.6
13.5
14,1
13.8
15.3
12.4
13.0
11.5
na
na
na
13.4
32.8
13.5
na
13.3
15.0
12.2
na
na
na
na
12.7
15.4
na
na
14.5
na
17.2
na
13.7
15.4
16.3 •
U.2
17.4
13.6
14,6
14.3
na
na
na
15.2
13.8
17.2
na
13.3
23.4
14.0
na
na
na
na
13.0
16.8
na
na
17.2
na
19.8
na
13.4
14.1
16.1
14.5
12.6
12.8
13.8
12.8
na
na
na
14.0
13.6
na
na
14.4
19.3
15.0
na
na
na
na
15.5
16.9
na
na
16.9
na
20.3
na
na
15.5
13.3
15,1
20,1
12.4
14.1
15.6
na
na
na
na
na
na
na
15.4
32.3
14.0
na
na
na
na
13.5
13.6
na
na
16.6
na
na
na
'na
11.1
14.2
12,3
9.9
8.1
10.7
10,0
na
na
na
na
na
na
na
12.0
15.6
12.1
na
na
na
na
12.3
12.1
na
na
14.8
na
na
na •= no data available.
D-47
-------
SUBCHRON1C TOXICiTY OF ORTHO-CRiSOL IN SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESDL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA (g/day)
ANIMAL NO. week 8 week 9 week 10 yeek 11 week 12 week 13
DOSE LEVEL
50 rng/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
.3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
14,1
13.0
13.4
18.0
13.8
16. 6
12.2
16.6
19.9
15.3
4.0
14.0
13.7
14.8
na
na
na
na
na
na
na
na
na
na
13.8
12.0
13.8
16.2
13.8
14.4
13.4
12.5
12.3
12.9
14.5
17.0
12.3
15.6
12.0
15.5
15.8
14.6
12.4
16.6
14.8
14.7
14.4
19.2
14.4
. 17.0
12.3
17.2
18.4
17.8
14.8
14.4
16.2
16.7
na
na
na
na
na
na
na
na
na
na
15.1
12.6
16.2
15.9
16.4
13.1
20.0
13.5
13.0
18.3
15.0
1.5
13.5
14.8
8.8
18.1
15.6
15.0
12.8
16.2
15.6
14.7
14.9
17.7
14.9
18.4
12.9
18.1
16.2
16.5
15.1
14.5
16.9
17.5
na
na
na
na
na
na
na
na
na
na
14.9
9.9
13.0
15.1
28.0
14.3
13.3
13.8
10.3
12.7
14.0
15.3
12.0
14.3
13.6
18.9
14,8
14.2
13.4
14.7
15.4
14.4
14.0
17.6
13.3
15.9
12.9
17.5
15.1
16.1
15.0
11.4
17.0
18.0
na
na
na
na
na
na
na
na
na
na
13.1
9.9
13.7
16.5
16.2
14.3
23.0
12.6
10.8
13.8
13.4
16.7
12.4
14.3
13.9
17.9
13.3
13.4
12.5
13.3
14.1
13.2
14.9
17.1
14.3
16.4
12.1
15.2
15.7
16.8
14.2
10.8
16.2
17.2
na
na
na
na
na
na
na
na
na
na
13.5
10.8
14.3
12.9
15.9
15.4
13.2
9.4
16.1
12.6
16.7
11.2
13.0
14.3
12.9
18.2
14.4
13.8
13.3
14.8
14.7
12.3
14,3
17. a
14.2
17.7
12.3
15.9
16.0
17.8
14.9
14.0
18.5
15.9
na
na
na
na
na
na
na
na
na
na
13.4
11.5
14.5
16.9
17.4
13.5
13.1
13.9
13.3
13.2
15.6
13.6
12.8
15.1
11.5
15.5
14.3
13.9
13.0
14.4
na = no data available.
D-49
-------
SUBCHRQN1C TQXICITT OF QRTHQ-CRESQL IN SPRAGUE DAWLEY RATS
FEMALE FOOO CONSUMPTION DATA (g/day)
AH1MAL NO. week 8 week 9 week 10 week 11 week 12 week 13
DOSE LEVEL
600 sig/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
312?
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
12.6
18.5
13.0
na
na
na
na
11.7
12.4
na
na
16.0
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
12.5
16.3
13.5
na
na
na
na
12.7
15.8
na
na
14.6
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na'
na
na
13.8
16.3
12.5
na
na
na
na
12.4
16.9
na
na
14.9
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
14.4
15.5
12.6
na
na
na
na
12.8
17.5
na
na
15.1
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
14.5
16.8
12.8
na
na
na
na
13.8
14.1
na
na
15.2
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
10.7
15.3
11.7
na
na
na
na
11.5
14,6
na
na
14.8
na
na
na = no data available.
D-50
-------
SUBCHRONIC TOXIC1TY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOCO CONSUMPTION DATA (g)
[Feeder Ueights]
ANIMAL HO. new 1 old 1 neu 2 old 2 new 3 old 3
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3D41
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
457
465
501
462
487
428
450
453
432
467
423
437
418
413
395
340
345
400
388
40S
394
375
392
367
433
372
370
356
340
437
408
370
399
404
384
414
374
386
388
395
385
392
418
419
358
404
353.5
344.9
399.1
342.8
357.7
315.6
339.2
344.4
303.5
372.4
321.2
340,6
289.9
300.6
269.1
235.1
239.1
290.8
283.0
290.5
296.9
281.2
299.1
266.7
311.1
279.6
261.3
258.7
236.4
320.7
302.6
277.1
294.8
291.9
273.4
313.9
270.8
296.3
299.0
282.3
380.1
271.9
307.9
313.2
254.7
310.7
704.1
684.0
673.0
718.5
694.4
695.3
712.1
689.4
682.8
715.4
587.6
587.1
739.4
634.5
666.5
704.5
571.3
590.0
597.4
663.9
580.6
578,5
598.1
589.2
739.4
598.8
588.8
588.7
612.2
723.2
659.0
670.2
678,1
698.1
581.9
695.7
714.9
655.7
680.5
592.6
701,5
668.3
662.4
694.2
566.8
712.7
583^9
571.1
572.8
554.3
548.7
565.2
587.9
559.5
552.7
604.5
458.3
569.8
588.2
550.8
418.2
565.9
452.7
470.8
536.7
490.7
462.7
492.8
472-8
491.7
640.0
437.0
484.5
511.0
607.8
506.0
546.3
569.1
565.9
575.0
458.2
582.7
558.4
600.8
577.0
464.9
583.8
542.2
526.8
580.7
458.0
596.3
583.9
571.1
572.8
554.3
548.7
565.2
587.9
559.5
552.7
604.5
518.7
569.8
588.2
550.8
509.3
565.9
452.7
470.8
536.7
490.7
462.7
492.8
472.8
535.2
640.0
520.1
4S4.5
511.0
607.8
607.8
546.3
569.1
565.9
575.0
458.2
582.7
558.4
600.8
577,0
464.9
583.8
542.2
526.8
580.7
458.0
596.3
400.0
461.6
474.2
422.2
385.4
444.5
470.6
444.5
455.6
503.5
398.0
466.2
279.8
445.6
437.7
397.4
338.4
361.7
431.6
370.1
354.6
354.4
375.7
377.2
518.6
418.9
392.1
381.6
415.8
507.5
442.4
47D.2
452.0
471.2
338.3
483.3
492.5
460.1
488.7
345.2
483.6
427.4
395.3
473.5
351.6
486.7
D-51
-------
SUBCHRONIC TOXICITY OF QRTHQ-CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUKPTION DATA (g>
[Feeder Weights]
ANIMAL NO. new 1 old 1 neu 2 old 2 new 3 old 3
DOSE LEVEL
50 mg/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071 '
3072
3073
3074
3075
175 rag /kg/day 3079
3080
3081
3082
3083
3084
3085
30 86
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
342
355
359
365
416
367
384
352
340
354
388
370
402
360
373
365
328
360
335
379
379
422
354
338
389
360
370
380
352
368
382
359
379
367
368
383
379
346
360
346
353
346
362
365
245.0
251.9
257.5
238.8
306.0
256.5
302.0
254.9
243.8
229.0
279.5
272.1
28S.9
250.6
265.3
257.3
218.5
262.7
232.6
272.2
276.2
302,3
258.2
223.4
267.4
263,1
249.2
269.0
238.8
264.2
277.0
239.8
281.2
262.4
267.4
252.6
285.9
226.6
209.9
224.0
235.4
233.3
248.9
227.5
608.0
564.8
606.4
589.9
641.0
575.1
603.3
607.6
566.4
618.4
587.5
600.9
600.5
564.1
575.6
602.4
581.2
593.1
553.8
573.8
601.3
574.3
551.6
518.7
562.2
588.2
548.3
588.0
569.7
533.8
606.0
600.4
578.2
573.8
565.0
583.7
565.3
575.1
579.6
575.9
616.9
532.4
590.5
569.9
484.2
4843
453.2
486.4
466.8
444.0
501.2
491.9
477.4
463.9
461.8
486.9
43B.2
475.1
450.0
477.0
428.2
494.1
446.8
466.8
499.8
483.0
447.9
474.9
483,6
424.5
465.9
460.3
421.3
489.6
489.6
479.1
477.9
464.5
458.2
457.8
458.5
460.1
461.3
505.1
488.6
417.0
485.2
445.4
484.2
484.3
453.2
486,4
466.8
444.0
501.2
491.9
477.4
505.9
461.8
486.9
519.5
475.1
450.0
477.0
428.2
494.1
446.8
446.8
499.8
483.0
447.9
474.9
483.6
424.5
465.9
460.3
421.3
489.6
421.6
479.1
477.9
464.5
458.2
457.8
458.5
460.1
461.3
505.1
488.6
417.0
485.2
445.4
336.4
369,3
330,2
361,5
333,2
317,6
396.9
375.9
367.3
364.1
346.8
379.4
399.4
356.6
360.8
339.8
269.4
393.6
345.3
361.0
412.6
394.8
357.1
290.7
355.0
390.9
316.4
347.7
317.3
312.1
382.2
341.1
381.4
372.8
356.3
343,0
359.9
350.4
367.2
278.6
381.0
380.7
325.9
338.9
D-52
-------
SU3CHSONIC TOXICITY OF ORTHO-CRESOL IN SPRACUI DAULEY RATS
FEMALE FOOD CONSUMPTION DATA Cg)
[Feeder Weights]
ANIMAL NO. new 1 old 1 new 2 old 2 new 3 old 3
DOSE LEVEL
600 mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
385
358
386
387
354
386
399
371
375
na
389
350
378
370
380
393
363
356
404
395
406
342
351
398
380
391
364
398
364
372
301.8
269.6
278,6
278.2
254.6
275.6
309.7
270.9
277.7
na
292.0
263.8
284. 1
289.9
2B4.4
na
258,3
244.8
336.2
301.2
317.8
256.9
270.7
305,8
271.5
286.5
276,4
294.6
280.3
233.3
589.1
555.3
593.1
570.1
151.8
567.3
582.1
619.3
590.9
na
584.8
556.2
543.2
592.6
615.5
na
578,4
535.7
589.0
603.1
610.8
546.1
549.7
567.2
582.6
588.7
586.9
579.9
595.7
640.8
486.4
458.4
484.6
452.0
446.1
450.4
490.9
492.5
482.7
na
475.5
463.3
444.2
501.2
510.3
na
480,7
412.1
490.5
503.7
511.4
443.3
480.3
472.9
456.3
538.5
585.2
464.1
502.1
510.7
486.4
458.4
484.6
452.0
446.1
450.4
490.9
492.5
482.7
na
475.5
463.3
444.2
501.2
510.3
na
480,7
412.1
490.5
503.7
na
na
480.3
472.9
456.3
na
na
464.1
502.1
510.7
na
384.0
390.4
353.2
349.5
343.0
404,4
401.3
402.4
na
na
na
350.1
271.5
415.6
na
387.8
307.4
404.9
na
na
na
na
383.8
348.4
na
na
362.3
na
390.6
na = no data available.
D-53
-------
SUSCHRCNIC TOXICITY OF ORTHO'CRESOL IN SPRAGUE DAUIEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Heights]
ANIMAL NO. new 4 old 4 new 5 old 5 new 6 old 6
DOSE LEVEL
0 ing/kg/day
50 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
302Z
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
438.3
422.3
421. 0
425.9
430.6
426.2
426.4
424.4
422.9
427.6
419.6
420.0
439.8
420.0
423.5
428.7
422.8
424.6
440.8
426.6
421.2
423.9
422.9
425.1
441.9
421.9
423.0
431.3
423.5
452.0
458.5
453.4
424.7
446.8
417.8
425.1
425.6
421.5
436.4
416.6
437.4
410. 8
435.1
432.7
422.4
419.8
313.3
306.4
326.3
259.9
274.8
311.8
313.1
313.3
312.5
315.4
310.2
322.5
269.9
304.8
292.7
312.8
306.2
320.8
335.9
300.8
312.7
319.6
318.3
320.9
306.0
311.0
312.8
306.9
325.4
348.4
356.9
352.7
317.8
336.9
307.4
320.4
309.5
323.4
343.2
234.8
340.6
302.7
303.9
331.2
321.7
309.2
526.4
497.1
467.6
509.6
494.2
471.1
467.2
490.5
502.1
501.3
470.9
487.2
481.9
467.0
478.5
470.9
479.8
494.3
491.2
481.8
491.4
482.7
490.5
472.8
495.2
475.6
457.4
464.1
468.0
470.7
466.5
461.8
469.2
468.9
467.9
454.2
451.8
474.1
460.2
445.6
494.4
481.3
467.3
466.8
469.2
495.8
406^5
356.5
364.2
380.6
355.0
356.4
349.6
378.2
394.6
408.1
354.3
389.6
282.3
370.9
343.0
363.4
361.1
396.4
387.5
355.6
396.5
374.0
390.2
372.8
370.4
362.9
332.2
347.6
365.2
373.3
368.2
358.8
349.3
257.7
357.2
350.0
346.1
379.0
363.7
330.8
395.6
360.9
346.7
358.8
368.5
377.4
494.5
470.8
450.2
485.1
471.0
482.9
480.8
475.5
452.2
463.1
450.4
478.6
503.8
480.3
431.0
453.1
448.7
470.3
476.7
464.9
487.0
481,2
495.1
485.3
513.3
469.7
467.5
485.4
483.5
455.5
468.9
480.3
456.7
514.6
476.4
479.9
473.3
465.7
466.2
460.1
505.2
479.0
449.0
499.9
471.2
491.4
385.7
361.7
345.6
341.5
319.4
377.9
373.5
355.6
349.7
365.6
341.3
375.0
314.9
282.9
296.9
339.3
323.7
373.4
365.0
342.0
381.0
375.5
393.4
392.2
394.1
355.1
352.6
362.0
376.3
352.6
372.6
377.7
337.4
418.1
365.0
396.6
364.3
369.6
359.0
319.2
397.9
364.4
322.5
388.1
360.5
381.3
D-54
-------
SUBCHRQN1C TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
AHIHAL NO- new 4 old 4 new 5 old 5 new 6 old 6
DOSE LEVEL
50 mg/kg/day 3062
Ccontinued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
423
419
415
424
435
442
422
420
415
424
419
414
423
414
448
469
441
446
476
479
448
441
463
433
431
433
406
456
431
437
480
449
466
466
439
413
444
443
441
420
434
431
431
438
.6
.4
.4
.0
.2
.8
.6
.1
.7
.9
.3
.4
.9
.0
.0
.9
.9
.8
.2
.7
.5
.4
.8
.6
.1
.0
.0
.3
.5
.3
.7
.2
.7
.7
.6
.4
.8
.1
.0
.9
.8
.9
.6
.4
320
.6
309.3
309
288
332
296
325
302
233
298
311
303
292
292
315
350
286
340
360
371
353
350
369
326
305
347
295
348
295
328
370
348
366
366
338
282
336
318
341
209
313
320
366
322
.8
.4
,6
,9
,7
.2
.7
,9
,3
.2
.5
.5
.4
.8
,5
.2
,0
.2
.2
.3
.0
.6
.3
.5
.7
.6
.0
.4
.6
.7
.3
.8
.1
.2
.8
.8
.1
.7
.2
.2
.0
.9
485.
443.
463.
456.
478.
459.
453.
472.
474.
467.
452.
448.
447.
483.
546.
469.
477.
494.
454.
469.
440.
471.
478.
440.
422.
439.
418.
459.
423.
461.
481.
410.
442.
423.
431.
440.
429.
421.
446.
423.
414.
412.
447.
423.
8
2
1
0
6
a
4
3
0
9
5
2
4
5
4
9
3
2
1
9
4
0
6
5
9
2
1
5
7
4
9
4
4
8
0
9
9
9
7
8
5
4
3
3
366.2
333
351
318
368
335
365
354
359
348
346
350
319
361
432
362
33"0
399
332
361
346
382
388
333
307
349
303
337
274
351
371
305
341
318
317
318
327
312
355
246
302
311
337
297
.1
.5
.6
.3
.4
.5
.9
.2
.3
.9
.7
.3
.9
.8
.2
.8
.7
.8
.4
.0
.0
.7
.2
.7
.5
.4
.9
.9
.5
.8
.3
.2
.8
.7
.7
.3
.3
.3
.5
.4
.9
.8
.9
482.4
467
474
465
496
470
464
488
488
479
455
496
465
474
476
469
464
475
472
492
458
481
489
481
453
493
457
485
471
485
473
455
454
487
483
471
473
497
481
485
517
443
483
501
.2
.9
.8
.5
.9
.8
.4
.2
.2
.5
.4
.1
.8
.6
.6
.9
.5
.6
.8
.9
.5
.2
.2
.6
.8
.7
.7
.8
.9
.6
.0
.6
.5
,8
.5
.4
.0
.6
.6
.5
.0
.7
.1
367.7
351.5
361.0
324.3
383.3
350.7
. 372.2
363.6
364.7
349.7
343.4
392.9
322.8
344.1
376.7
363^2
333.9
371.9
355.4
372.8
355.7
375.7
389.8
380.5
332.3
402.1
340.5
358.0
363.5
373.5
369.5
355.3
351.5
381.2
373.8
343.1
374.1
379.1
381.7
324.5
393.8
375.3
389.1
373.0
D-55
-------
SUBCHRON1C TOXICITT OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO, new 4 old 4 new 5 old 5 new 6 old 6
DOSE LEVEL
6DO mg/kg/day 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
na
438,9
434.0
426.8
433.3
415.0
443.9
430.2
457,2
na
na
na
462,2
418.3
423.8
na
419.9
430.4
425.5
na
na
na
na
415.4
425.4
na
na
428.1
na
' 432.7
na
342.7
326.1
312.7
334.2
293.2
348.4
327.7
357.2
na
na
na
355.6
321.4
303.2
na
326.5
266.9
327.5
na
na
na
na
324,3
307.7
na
na
308.0
na
294.3
na
427.8
428.6
406.0
407.2
435.2
441.1
424.1
451.8
na
na
na
439.1
428.6
398,6
na
405.5
437,2
417.9
na
na
na
na
430.8
433.9
na
na
409.1
na
410.7
na
333.9
329.9
293.5
305.9
347.3
351.6
327.8
362.2
na
na
na
341.2
333.5
na
na
304.6
302.0
312.8
na
na
na
na
322.4
315.6
na
na
291.1
na
268.3
na
na
475.2
470.0
484.9
474.3
476.0
451.5
470.6
na
na
na
na
na
na
na
464.2
463.6
464.0
na
na
na
na
445.9
489.7
na
na
506.2
na
na
na
na
367.0
377,!
379.3
333.4
389,1
352,6
361.3
na
na
na
na
na
na
na
356,5
237,6
365,7
na
na
na
na
351.1
394.2
na
na
390,3
na
na
na = no data available.
D-56
-------
SU3CHRQNIC TOXIClTf Of ORTH -CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. new 7 old 7 new 8 old 8 new 9 old 9
DOSE LEVEL;
0 mg/kg/day 3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
50 mg/kg/day 3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
385.7
361.7
370.3
341.5
368.1
377.9
373.5
355.6
349.7
365.5
442.8
506.5
433.4
474.0
483.9
432.2
432.7
473.8
477.8
434.0
455.4
450.3
476.8
451.2
470.4
418.2
447.1
434.3
428.6
460.8
405.3
377.7
367.8
418.1
365.0
396.6
391.8
369.6
359.0
424.6
566.0
50t. 2
469.4
515.5
454.3
487.9
358.8
337.9
339.9
310.2
329.2
344.9
344.7
327.3
322.4
346.8
345.7
414.6
278.8
380.8
361.1
338.3
342. 2
388.3
386.1
330.9
354.2
356.8
383.9
367.0
356.4
325.6
341.7
338.3
336.6
369.5
350.7
374.4
325.6
321.7
376,9
348.9
370.8
358.1
343.1
393.7
471.6
390.1
373.8
414.6
356.1
391.0
na
na
na
na
na
na
na
na
na
na
441.6
463.3
422.4
459.3
441.1
426.0
412. 1
434.6
460.7
422.6
428.1
424.1
420.0
420.9
442.2
414.3
425.5
401.6
412.6
428.8
na
na
na
na
na
na
na
na
na
na
471.6
424.4
430.2
433.3
435.3
440.9
na
na
na
na
na
na
na
na
na
na
348.3
381.9
292.6
367.0
322.0
331.7
311.6
348.5
358.4
308.2
335.6
331.2
321.3
336.4
327.7
318.3
327.1
308.6
318.7
338.7
na
na
na
na
na
na
na
na
na
na
382.7
314.3
307.6
328.5
346.3
346.6
na
na
na
na
na
na
na
na
na
na
443.8
452.1
480.6
452.4
434.6
467.1
442.1
429.3
449.2
450.1
460.1
510.8
490.4
444.7
463.1
479.0
440.1
436.8
445.6
437.8
na
na
na
na
na
na
na
na
na
na
466.3
442.1
455.9
463.2
455.6
421 .B
na
na
na
na
na
na
na
na
na
na
349.8
367.2
314.4
348.0
315.5
363.5
339.9
348.7
352.8
340.3
358.1
424.6
396.8
352.2
363.3
387.9
340.5
337.3
356.3
344.4
na
na
na
na
na
na
na
na
na
na
377.1
313.8
332.8
352.2
362.5
316.7
na = no data available.
D-57
-------
SUBCHRON1C TOXtClTY OF ORTH -CRESOL JN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA (i)
[Feeder Weights]
ANIMAL NO. new 7 old 7 new 8 old 8 new 9 old 9
DOSE LEVEL
50 mg/kg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3Q83
3084
3085
3086
3087
3088
3039
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
31 D6
3107
3108
444.
2
437.7
461.
432.
480.
478.
456.
1
6
5
1
6
461 .9
474.
462.
474.
467.
434.
441.
446.
363.
333.
371.
355.
372.
355.
375.
389.
380.
452.
455.
443.
462.
451.
434.
465.
428.
445.
461.
455.
434.
442,
472.
467.
425.
449.
6
9
1
3
8
1
1
2
9
9
4
8
7
7
8
5
1
3
0
8
B
5
6
6
1
9
8
1
7
7
6
2
1
451.8
437.
450.
1
4
337.2
334
351
310
374
356
369
347
364
364
371
376
324
325
414
330
294
349
322
332
356
347
322
352
365
372
345
354
356
345
361
342
355
366
363
321
359
371
373
328
352
368,
359,
342,
.6
.3
,6
.3
.4
.3
.8
.3
.9
.2
.9
.1
.5
.7
.1
.7
.9
.4
.1
.9
.4
.0
.4
.8
.3
.9
.9
.5
,2
.9
.2
.2
.9
.6
.9
.2
.3
.2
.2
.9
.3
.9
.2
419
413
416
406
415
408
415
419
418
416
41Z
416
421
413
425
420
422
413
434
443
475
423
432
.431
430
415
424
439
438
428
.6
.1
.3
.4
.a
,2
.1
.5
.0
.2
.7
.5
.3
.1
na
na
na
na
na
na
na
na
na
na
.6
.9
.3
.2
.7
.3
.9
.1
.7
.2
.1
.3
.9
.9
.9
.7
428.3
432.2
429.6
421.3
320
3n
322
280
.9
.,9
.8
.6
318.5
290
329
303
279
308
.8
.4
.3
.0
.8
384.7
318
325
309
329
.4
.4
.5 "
na
na
na
na
na
na
na
na
na
na
.2
337.1
325
299
338
342
382
335
346
341
328
296
338
331
354
320
317
330
343
305
.4
.5
.3
.3
.0
.3
.8
.2
.4
.2
.7
,0
.8
,2
.4
.1
.0
.3
458.5
443,5
407.7
417.2
411.0
417.2
428.5
410.5
438.9
412.4
411.8
418.7
382.6
419.5
na
na
na
na
na
na
na
na
na
na
502.9
497.9
492.0
530.9
534.7
515.7
505.1
517.9
503.4
527.9
478.5
427.2
510.8
471.0
530.2
492.1
496.5
525.0
483.3
453.0
354
345
307
282
309
298
342
290
309
287
308
317
269
302
.9
.3
.2
.6
.9
.1
.3
.3
.9
.9
.5
.8
.0
.9
na
na
na
na
na
na
na
na
na
na
396.9
410
.0
37S.7
419
419
423
365
423
412
400
373
416
416
367
465
365
387
420
393
339
.5
.7
.8
.4
.6
.1
.1
.6
.8
.0
.3
.6
.5
.2
.3
.7
.9
na = no data available.
D-58
-------
SUBCKRONiC TOXICITY OF ORTH -CRESOL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA
-------
SUBCHRON1C TOXICITY OF QRTHO-CRESOl IN SPRACUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA
-------
SUBCHRON1C TOX1CITY OF ORTKO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights)
ANIMAL NO. new 10 old 10 ney 11 old 11 ney 12 old 12 new 13 old 13
DOSE LEVEL
50 mg/'tcg/day 3062
(continued) 3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
1093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
437. Z
445.4
423.8
411.9
424.5
421.1
426.7
425.7
431.0
432.2
422.4
422.5
415.1
434.3
na
na
na
na
na
na
na
na
na
na
452.8
428.3
422.7
416.0
449.0
423.8
426.2
452.9
448.8
435.1
448.8
432.3
436.1
456.9
448.2
461.6
460.8
424.2
434.0
425.1
328.0
342.7
319.5
308.2
320.2
292.5
336.4
298.9
317,4
317.0
316.4
320.6
296.5
311.8
na
na
na
na
na
na
na
na
na
na
348.3
358.8
331.4
310.0
253,2
323.7
333.3
356.1
376.5
346. 0
351.1
325.3
351.9
357.0
353.1
329.0
357.5
324.7
340.2
321.9
439.3
437.1
427.2
432.5
432.4
436.4
430.2
432.8
430.9
432.1
434.2
433.1
428.6
432,0
na
na
na
na
na
na
na
na
na
na
428.8
425.0
427.4
426.5
435.5
432.1
423.4
425.9
426.3
426.9
426.2
426.7
424.3
426.6
425.3
429.7
427.8
427.5
425.6
425.9
331.5
336.3
329.3
309,1
339.5
325.1
339,6
310.0
325. 4
319.2
329.2
353.1
309. 5
306. 3
na
na
na
na
na
na
na
na
na
na
336.9
355,9
331.2
310.8
321.8
332.1
262.5
337.8
350.8
330.1
332.6
309.9
337.8
326.5
327.8
304.7
334.5
333.4
338.0
332.8
459.8
430.9
422.0
425.6
446.4
428.6
440.8
453.7
438.8
454.2
440.8
456.6
444.4
461.4
na
na
na
na
na
na
na
na
na
na
425.9 ,
439,3
455.2
445.6
447,9
432.7
458.3
446.7
422.8
462.8
452.5
443.2
468.6
447,0
482.1
434.2
467.1
476.4
458.8
434.7
361.1
338. 3
318. 0
305.8
346.6
313,5
356.2
347.2
329.2
336.6
341.4
381.2
330.7
341.2
na
na
na
na
na
na
na
na
na
na
331.1
363.9
355.0
355.6
336.3
324.7
366.1
381.1
310.4
374.7
335.7
364.5
377.9
346.9
392.0
306.9
366.2
379.8
365.4
331.2
409.2
444,5
452.3
431.0
435.2
453.4
422.5
441.5
426.9
441.8
476,2
483.1
494.1
488.3
na
na
na
na
na
na
na
na
na
na
412.3
459.2
456.1
451.0
472.5
459.6
445.4
455.1
482.4
455.3
541.3
548.2
522.6
448.5
543.1
506.2
568.3
508.3
442.8
416.1
321.0
354.6
352.2
306,7
335.5
329.4
336.7
330.5
315.2
317.0
371,8
385.4
364.7
376.7
na
na
na
na
na
na
na
na
na
na
318.4
378.7
369.1
349.7
368,2
378.7
366.5
371.7
389.6
376.0
432.0
452.8
433.2
342.9
462.8
397.9
482.2
424.7
351.8
329.5
na - no data available.
D-61
-------
SUBCHRCNIC TQXICJTY OF QRTHQ-CRESQL IN SPRAGUE DAULEY RATS
FEMALE FOOD CONSUMPTION DATA (g)
[Feeder Weights]
ANIMAL NO. ney 10 old 10 n«y 11 old 11 new 12 old 12 ney 13 old
DOSE LEVEL _______ _ . .
600 mg/kg/day ' 3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
312?
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
415.5
414.4
427.8
na
na
na
na
418.4
410.9
na
na
400.3
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
318,9
300.4
340,6
na
na
na
na
331.9
292.4
na
na
295.8
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
420.4
416.9
423.2
na
na
na
na
421.5
413.2
na
na
422.2
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
319.6
308.5
335.0
na
na
na
na
331.9
290.7
na
na
316,4
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
421.9
431.9
439.6
na
na
na
na
453.4
420.2
na
na
439.5
na
na
na
na
• na
na
na
na
na
na
na
na
na
na
na
na
na
na
320.4
314.5
350.3
na
na
na
na
356.9
321.8
na
na
332.8
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
423.3
432.3
412.1
na
na
na
na
438.9
471,5
na
na
465.2
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
348.4
325.4
341.9
na
na
na
na
370.1
383.6
na
na
376.7
na
na
na = no data available.
D-62
-------
SUBCHRONiC TOXIC1TY OF OSTHO-CRESOL IN SPRAGUE DAWLEY RATS
MALE HEMATQLQGY VALUES
[Interim Sacrifice]
DOSE LEVEL
0 mg/kg/day
ANIMAL NO. RiC HGB
(x 1Q*6/mnf3) (g/dl)
HCT PT APTT RETIC
(sec.) (see.) (% rbc)
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2881
2882
2883
2884
2885
2886
2887
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
8.16
7.91
7,89
7.13
7.47
7.95
7.63
8.27
7.98
6.27
7.79
8.89
8.85
8.79
8.18
7.76
7.55
7.44
7.64
8.08
8.07
8.52
8.32
7.80
7.63
7.81
7.74
7.70
7.96
7.82
7.64
7.91
7.83
7.13
dead
7.28
7.43
8.18
7.60
8.79
15.7
16.1
16.2
15.2
14.9
15.6
14.7
16.0
15.7
15.7
15.2
17.3
17.0
16.1
15.8
14.7
15.0
14.8
15.0
16.1
15.4
15.8
16.3
15.3
14.5
15.4
15.3
15.4
15.0
15.6
14.8
15.5
15.1
14.8
dead
15.9
15.0
15.9
14.6
16.1
42.6
44.3
46.7
40.7
41.0
44.1
40.6
45.5
45.6
43.7
43.0
48.8
45.5
48.5
43.1
40.4
43.6
40.5
43.0
46.1
44.1
46.0
47.3
42.5
42.2
43.6
44.9
44.5
43.9
45.0
42.4
43.1
44.5
41.0
dead
45.1
42.5
46.3
42.3
47.0
11.9
11.0
10.9
12.5
12.3
11.5
11.6
11.9
12.2
12.3
12.0
13.3
13.0
11.1
13.3
11.5
10.3
11.6
10.4
10.9
11.7
11.8
13.0
11.4
11,8
Z
10.5
13.0
12.4
11.7
11.8
11.5
12.0
12.2
dead
10.3
10.7
11.3
11.4
11.3
28.8
30.9
29.3
31.5
30.6
33.6
30.9
28.8
34.0
27.9
30.9
35.3
34.9
34.5
33.2
31.1
35.1
28.1
39.0
37.0
34.7
29.0
35. Z
31.5
30.3
2
35.2
35.9
33.5
30.7
30.6
30.7
34.9
31.0
dead
36.3
30.3
30.7
34.0
34.6
0.9
0.9
1.0
0.8
0.9
0.6
1.0
0.5
0.9
1.6
0.8
0.4
0.9
0.9
0.1
1.2
1.3
0.5
0.6
0.1
0.5
0.5
0.2
• 1.4
1.3
0.1
1.0
1.5
0.5
0.6
2.0
0.5
0.8
0.2
dead
0.4
0.7
1.8
0.3
0.8
D-63
-------
SUSCHRONtC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWIEY PATS
MALE HEMATQLQGY VALUES
[Interim Sacrifice]
ANIMAL NO.
UBC
DOSE LEVEL
0 mg/kg/day
SEGS SANDS LYMPHS MONO EOS
% wo <% WBO c% wso c% wso <% weo
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2881
2882
2883
2884
2885
2886
2837
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
. 2951
295 Z
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
13.4
12.9
17.1
19.9
16.7
18.9
17.1
22.8
15.0
13.0
11.7
16.8
16.2
14.4
9.4
15.3
14.7
11.8
13.3
22.5
12.4
11.6
15.8
17.5
15.5
14.5
12.5
18.2
14.6
9.4
16.3
13.0
15.1
18.2
dead
11.7
14.4
17.8
12.2
14.1
3
6
6
9
8
6
18
10
5
10
7
6
18
2
6
8
9
13
11
15
7
15
8
6
15
22
9
15
6
12
20
12
19
10
dead
16
11
4
15
7
0
0
0
1
2
0
0
0
0 .
0
0
3
1
0
0
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
1
0
0
0
dead
0
0
0
1
0
95
92
94
89
89
92
79
90
90
90
90
90
80
94
89
83
87
83
85
85
85
83
92
89
77
74
87
83
92
87
76
86
77
85
dead
80
85
95
83
91
1
1
0
1
1
1
1
0
4
0
Z
1
1
0
5
4
4
1
2
0
5
2
0
5
2
3
3
0
1
1
3
1
1
5
dead
3
4
0
0
1
1
1
0
0
0
1
2
0
1
0
1
0
0
4
0
4
0
3
2
0
3
0
0
0
0
1
0
2
1
0
0
1
3
0
dead
1
0
' 1
1
1
D-64
-------
SUSCHRONIC TOXIC1TY OF QRTHC-CRESCL IN SPRAGUE PAWUY RATS
MALE HEMATOLOGY VALUES
[Interim Sacrif ice]
DOSE LEVEL
0 mg/kg/day
ANIMAL NO. UBC SEGS BANDS
(x 10A3/imr"3> Cx 10*3/nnT3> Cx 10*3/nrrr3)
LYMPHS
MONO
EOS
50 rog/kg/day
175 mg/kg/day
600 mg/ltg/day
(x
2881
2882
2883
2884
2885
2886
28S7
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
13.4
12.9
17.1
19.9
16.7
18.9
17.1
22.8
15.0
13.0
11.7
16.8
16.2
14.4
9.4
15.3
14.7
11.8
13.3
22.5
12.4
11.6
15.8
17.5
15.5
14.5
12.5
18.2
14.6
9.4
16.3
13.0
15.1
18.2
dead -
11.7
14.4
17.8
12.2
14.1
0.4
o.a
1.0
1,8
1.3
1.1
3.1
2.3
0.8
1.3
0.8
1.0
2.9
0.3
0.6
1.2
1.3
1.5
1.5
3.4
0.9
1.7
1.3
1.1
2.3
3.2
1.1
2.7
0.9
1-1
3.3
1.6
2.9
1.8
dead
1.9
1.6
0.7
1.8
1.0
0.0
0.0
0.0
0.2
0.3
0.0
0.0
0.0
0.0
0.0
0.0
0.5
0.2
o.o
0.0
0.2
0.0
0.0
0.0
0.0
o.o
o.o
0.0
0.0
o.o
0.0
0.1
0.0
0.0
0.0
0.2
0.0
0.0
0.0
dead
0.0
0.0
o.o
0.1
0.0
12.7
11.9
16.1
17-7
14.9
17.4
13.5
20.5
13.5
11.7
10.5
15.1
13.0
13.5
8.4
12.7
12.8
9.8
11.3
19.1
10.5
9.6
14.5
15.6
11.9
10.7
10.9
15.1
13.4
8.2
12,4
11.2
11.6
15.5
dead
9.4
12.2
16.9
10.1
12.8
0.1
0.1
0.0
0.2
0.2
0.2
0.2
0.0
0.6
0.0
0.2
0.2
0.2
0.0
0.5
0.6
0.6
0.1
0.3
0.0
0.6
0.2
0.0
0.9
0.3
0.4
0.4
0.0
0.1
0.1
0.5
0,1
0.2
0.9
dead
0.4
0.6
0.0
0.0
0.1
0.1
0.1
0.0
0.0
0.0
0.2
0.3
0.0
0.2
0.0
0.1
0.0
0.0
0.6
0.0
0.6
0,0
0.4
0.3
0.0
0.4
0.0
0.0
0.0
0.0
0.1
0.0
0.4
0,1
0,0
c.o
0.1
0.5
0.0
dead
•0.1
0.0
0.2
0.1
0.1
-------
SUBCHRONIC TOXICITY OF ORTHQ-CRESQL IN SPRAGUE DAWLEf RATS
MALE HEMATOLQGY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.
2891
2892
2893
2894
2895
2896
2897
2898
2399
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2963
2966
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
RBC
(x 10'6/nrT3)
8.26
8.90
8.65
8.67
8.71
8.35
8.70
8.27
9.09
8.62
8.65
8.23
8.88
9.30
8.36
8.02
8.78
8.89
8.18
8.23
8.24
8.05
8.54
8.49
8.19
9.43
9.35
8,58
8.25
8.60
8.72
7,88
dead
dead
8.20
dead
9.43
dead
8.15
9.11
HGB
(g/dl)
15.0
15.5
15.8
16.0
15.0
15.3
14.8
15.0
15.2
14.9
15.5
15.4
15.5
16.0
14.8
14.7
15.0
15.1
15.3
14.6
15.4
15.0
15.6
15.4
14.3
16.4
15,5
15.3
14.9
15.9
15.5
15.2
dead
dead
14.8
dead
16.0
dead
14.9
16.0
HCT
C/.)
43.2
44.1
45.4
45.0
41.0
43.4
42.8
42.6
43.7
41.6
43.6
43.7
41.9
46.4
41.4
43.3
42.3
44.8
42.2
39.6
44.0
42.8
44.7
43.1
42.5
47.5
45.2
42.5
42.8
46.1
44.6
43.7
dead
deed
41.6
dead
46.8
dead
42.6
44.4
PT
(sec.)
14.4
11.2
10.2
8.6
9.9
11.6
6. a
9.7
12.6
11.8
11.0
11.6
11.6
11.3
11.9
11.5
6.8
11.3
11.7
12.5
12.4
12.4
12.2
11.8
11.3
11.4
12.1
12. 7
13.8
11.7
15.1
14.4
dead
dead
11.1
dead
8.6
dead
8.1
6.8
APTT
Csec.)
44.6
34.0
34.2
27.5
33.9
3D. 5
38.0
31.6
35.5
34.5
29.3
34.3
32.3
33.0
35.8
38.3
33.1
36.1
33.0
33 .3
37.7
36.3
34.8
31.6
32.5
32.2
18.2
34.8
37.7
33.4
34.2
35.1
dead
dead
33.4
dead
35.2
dead
10.3
32,4
RET1C
(54 rbc)
1.1
1.1
0.8
1.1
0.6
1.1
0.4
0.5
1.8
1.0
0.5
0,9
0.4
0.4
1.1
0.7
0.5
1.9
3,3
1.2
2.7
2.1
1.6
3.0
0.7
0.3
0.8
0.5
1.6
1.7
0.5
0.5
dead
dead
4,0
dead
1.0
dead
0.2
1.9
D-GG
-------
SUBCHRONIC TOXICiTY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
MALE HEMATOLOGY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
ANIMAL NO, WBC SECS
(x 10A3/imT3) (% U8C)
BANDS LYMPHS MONO EOS
WBC) (% WBC) (% WBC) (% WBC)
50 mg/kg/day
175 rag/kg/day
600 mg/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
15.4
10.4
13.6
16.2
16.4
11. B
13.8
14,6
17.1
13.9
9.5
9.9
14.8
11.3
15,2
11.5
17.8
13.0
11.3
11.5
11.5
13.4
13.4
14.1
11.2
16.6
16.1
11.2
15.1
17.8
13.5
11.1
dead
dead
12.4
dead
11.9
dead
16.5
20.0
5
18
11
43
21
9
14
16
34
17
8
19
33
21
16
9
13
24
15
14
28
13
13
22
34
9
20
11
17
18
32
2
dead
dead
12
dead
24
dead
10
11
o.
0
0
1
1
1
2
0
0
1
0
0
1
0
2
0
1
1
1
0
0
0
0
2
1
0
0
0
0
0
1
1
dead
dead
0
dead
0
dead
0
1
92
80
89
54
77
88
82
80
63
79
88
72
61
78
76
85
84
73
75
84
70
82
84
74
62
88
79
85
77
81
65
84
dead
dead
85
dead
71
dead
87
65
3
0
0
1
1
2
2
1
2
1
3
9
5
0
6
5
3
1
9
2
2
3
3
2
1
1
1
2
6
0
1
12
dead
dead
3
dead
3
dead
3
2
0
1
0
1
0
0
0
3
1
2
1
0
0
1
0
1
0
1
0
0
0
2
0
0
1
2
0
2
0
1
1
1
dead
dead
0
dead
2
dead
0
1
D-G7
-------
SUBCKROHIC TOXIC1TY Of ORTHO-CRESQL IN SPRAGUE DAWLEY RATS
HALE KEHATOLOGY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.
2391
2892
2893
2894
2895
2396
2897
2898
2899
2900
2924
2925
2926
2927
2928-
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
wee
(x 10A3/mniA3)
15.4
10.4
13.6
16.2
16.4
11.8
13.8
14.6
17.1
13.9
9.5
9.9
14.8
11.3
15.2
11.5
17.8
13.0
11.3
11.5
11.5
13.4
13.4
14.1
11.2
16.6
16.1
11.2
15.1
17.8
13.5
11.1
dead
dead
12.4
dead
11.9
dead
16.5
20.0
SEGS
(x 10A3/iTfnA3
0.8
1.9
1.5
7. a
3.4
1.1
1.9
2.3
5.8
2.4
0.8
1.9
4.9
2.4
2.4
1.0
2.3
3.1
1.7
1.6
3.2
1.7
1.7
3.1
3.8
1.5
3.2
1.2
2.6
3.2
4.3
0.2
dead
dead
1.5
dead
2.9
dead
1.7
2.2
BANDS
) (x 1QA3/(imA3
0.0
0.0
0.0
0.2
0.2
0.1
0.3
0.0
0.0
0.1
0.0
0.0
0.1
0.0
0.3
0.0
0.2
0.1
0.1
0.0
0.0
0.0
0.0
0.3
0.1
0.0
0.0
0.0
0.0
0.0
0.1
0.1
dead
dead
0.0
dead
0.0
dead
0.0
0.2
LYMPHS
3
-------
SUBCHRONtC TOXICITY QF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE HEMATOLQGt VALUES
[Interim Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 (Tig/kg/day
600 mg/kg/day
ANIMAL NO,
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
RBC
8.18
7.79
7.84
8.01
7.92
7.97
8.33
7.79
8.20
7.79
8.28
7.70
7.99
3.18
7.83
7.28
8.42
7.67
.b
7.62
7.95
7.50
7.97
7.29
8.30
7.50
6.75
7.89
7.23
7.14
dead
dead
7.74
.a
7.90
7.59
8.12
7.15
7.79
dead
HGS
S3 (g/dl)
15.5
15.4
15.8
15.9
15.5
15,9
16,2
15.4
14.8
15.4
15.5
15.0
15.9
16.6
16.0
14.3
16.9
15.8
.b
15.5
16.2
15.8
14.8
14.9
16.2
15.1
14.6
14.8
15.8
14.9
dead
dead
15.1
,a
15.4
15.2
15.7
14.8
15.4
dead
HCT
43.5
43.5
44.3
45.8
44.5
45.0
46.8
43.7
42.2
43.2
44.2
42.2
45.8
44.6
44.4
39.8
46.2
40.0
.b
45.0
45.7
43.1
37.3
40.9
44.8
41.7
39.0
43.2
40.7
40,1
dead
dead
42.2
.a
44.4
43.2
44.5
41.1
43.5
dead
PT
Csec.)
10.0
10.7
11.4
11.2
11.0
11.1
12.1
10.8
10.3
11.2
10.3
11.5
11.5
11.2
10.7
10.9
10.8
10.6
10.3
9.6
10.9
11.6
8.0
11.3
11.0
11.2
11.4
11.3
10.3
12.1
dead
dead
Z
11.9
10.6
12.2
11.3
13.4
10.5
dead
A PIT
(sec.)
'36.6
33.7
27.3
35.7
29.3
36.2
33.3
32.9
40.1
48.1
38.3
33.7
42.8
32.0
29.4
32.5
29.8
33.2
34.8
32.7
32.6
29.9
34.2
36.5
32.8
28.2
33.0
37.0
30.5
45.4
dead
dead
Z
35.5
36.2
31.5
37.5
44.1
33.7
dead
RET1C
(% rbc)
1.6
0.4
1.2
0.7
2,3
0.3
0.1
0.9
0.1
0.1
0.1
O.T
0.6
1.8
1.0
0.7
0.5
1.0
0.7
0.3
0.7
0.5
1.5
0.5
0.7
0.8
0.5
0.7
0.3
0.1
dead
dead
4.0
.8
1.1
2.2
2.1
0.2
1.8
dead
88lood clotted
"Sample lost
D-G9
-------
DOSE LEVEL
SUBCHRON1C TOXICITY OF ORTHO-CRESOL IK SPRAGUE DAWLEY RATS
FEMALE HEHATOLOGY VALUES
[Interim Sacrifice]
ANIMAL NO. WBC SEGS BANDS LYMPHS HOMO EOS
(x 1Q"3/mmA3) (% WBC) (% UBC) (% UBC) (% U8C) (% U8C)
0 mg/kg/day
SO mg/kg/day
175 ing/kg/day
600 mg/kg/day
1
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082'
3083
3084
3085
3086
3087
3088
3112
3113
3114
3115
3116
3117
3118
3119
•3120
3121
13.7
9.7
7.5
10.9
14.2
9.0
8,5
13.1
13.0
9.5
11.6
9.6
11.8
24.8
9.9
13.4
12.1
10.6
na
10.4
16.2
13.1
9.9
12.6
11.3
10.2
11.6
12.1
10.2
13.7
na
na
14.9
na
13.0
20.0
11.1
13.8
9.7
na
9
8
5
14
9
12
8
7
13
7
8
17
8
15
8
2
32
6
17
4
14
9
6
16
4
1
25
13
14
11
na
na
10
na
30
7
10
17
8
na
1
0'
0
0
0
2
0
• o
0
0
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
na
na
0
na
0
0
1
1
0
na
as
90
94
82
89
85
86
,92
84
90
91
76
87
83
89
97
67
90
79
91
84
83
90
82
94
93
73
86
84
88
na
na
90
na
67
91
87
81 '
91
na
4
2
1
3
2
1
1
1
2
2
0
9
2
2
3
1
0
4
2
3
0
2
0
2
1
5
1
0
2
1
na
na
0
na
3
2
1
1
1
na
1
0
0
1
0
c
5
0
1
1
0
1
3
0
1
0
0
0
0
2
1
1
4
0
1
1
0
1
0
0
na
na
0
na
0
0
2
0
0
na
na = no data available.
D-70
-------
SUBCHRQNIC TQX1CITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE KEMATQLQGY VALUES
tlnterira Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 ing/kg/day
600 mg/kg/day
ANIMAL NO.
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3084
3085
3086
3087
3038
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
UBC
(x 10"3/imT3) (x
13.7
9.7
7.5
10.9
14.2
9.0 •
8.5
13.1
13.0
9.5
11.6
9.6
11.8
24.8
9.9
13.4
12.1
10.6
na
10.4
16.2
13.1
9.9
12.6
11.3
10.2
11.6
12.1
10.2
13.7
na
na
14.9
na
13.0
20.0
11.1
13.8
9.7
na
SEGS
1Q*3/mT3
1.2
0.8
0.4
1.5
1.3
1.1
0.7
0.9
1.7
0.7
0.9
1.6
0.9
3.7
0.8
0.3
3.9
0.6
na
0.4
2.3
1.2
0.6
2.0
0.5
0.1
2.9
1.6
1.4
1.5
ne
na
1.5
na
3,9
1.4
1.1
2.3
0.8
na
BANDS
) (x 10*3/^3)
0,1
0.0
0.0
0.0
0.0
0.2
0.0
0.0
D.O
0.0
0.1
0.0
0.0
0.0
0.0
0.0
0.0
0.0
na
0.0
0.2
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
na
na
0.0
na
0.0
0.0
0.0
0.1
0.0
na
LYMPHS
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE HEMATQIQGY VALUES
CTerminal Sacrifice]
DOSE LEVEL
0 nig/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.
3023
3024"
3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3053
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3128
3129
3130
3135
3136
3139
RBC
(x 10*6/mmA2
8.36
8.77
8.67
7.97
8,56
8.73
7.75
8.28
8.07
9.19
8.55
8.48
8.52
8.20
8.65
8.30
8.43
8.33
8.43
7.69
8.18
8.56
8.00
7,54
7.94
8.41
8.75
9.06
8.27
8.36
dead
dead
9.12
8.54
8.15
7.72
HG8
i) (g/dl)
16.3
15.7
16.3
15.3
16.0
16.2
14.3
15.9
15.2
16.5
16.0
15.6
15.3
15.1
16.6
16.1
15.6
16.3
15.8
15.3
15.2
15.2
15.5
14.0
14.5
15.4
16.2
16.2
15.3
16.1
dead
dead
16.4
15.4
15.5
15.2
HCT
(%)
45.5
44.3
45.3
41.4
46.3
45.3
3S.7
44.9
41.8
46.4
44.4
43.6
43.9
42.7
46.1
45.7
44.0
45.2
44.2
41.8
41.9
41.4
43,5
40.7
41.6
44.1
45.3
47.1
42.7
44.9
dead
dead
47.2
43.3
44.5
43.5
PT
(sec.)
12.3
9.8
11.3
11.4
11.3
10.4
10.9
10.3
11.1
10.3
12.9
8.3
10.8
11.4
10.1
12.2
10.8
11.1
11.0
11.4
8.1
11.8
9,7
10.6
12.7
12.5
10.9
12.5
10.9
6.5
dead
dead
10.5
11,2
10.4
10.8
APTT
(sec.)
34.5
21.4
31.4
35.5
46.1
34.0
33.5
32,5
29.1
31.3
38.0
33.2
36,8
29.2
27.4
36.1
32.7
33.3
30.4
34.8
41.1
43.6
34.7
39.9
40.2
38.3
15.4
36.9
35.0
36.1
dead
dead
49.8
30.5
31.9
33.4
8ETIC
<% rbc)
1.3
0.1
0.8
1.1
0.3
2.7
1.0
2.2
1.7
o.a
1.0
0.7
1.5
' 1.3
0.4
0.8
0.6
0.1
0.9
1.1
1.8
1.1
2.5
0.8
1.0
1.0
1,3
0.7
0.4
2.4
dead
dead
1.0
1.4
1.9
1.3
D-?:
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOl IN SPRAGUE DAULEY RATS
FEMALE HEMATQLOGY VALUES (% WBC)
[Terminal Sacrifice]
ANIMAL NO.
WBC
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
(x
SEGS BANDS LYMPHS
(% WBC) {% WBC) (% WBC)
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
, 3094
• 3095
3096
3097
3098
3128
3129
3130
3135
3136
3139
9.8
11.7
10.9
5.8
9.6
13.7
11.9
10.8
8.2
12.3
8.3
7.1
13.7
14.1
9,0
7.3
10.2
9.6
8.5
8.4
9.9
7.8
10.8
8.0
10,1
7.8
6.9
6.9
10.0
10,4
dead
dead
11.5
10.1
10.4
11.7
6
31
24
11
17
39
10
1C
20
7
16
16
13
19
14
13
15
13
13
11
19
11
10
24
11
18
10
22
14
20
dead
dead
5
8
39
27
0
2
2
0
0
0
0
1
1
0
1
3
0
1
0
0
0
0
5
1
0
0
0
0
2
C
2
0
2
0
dead
dead
0
0
0
0
88
62
70
87
77
58
87
89
76
90
79
76
85
79
85
86
85
84
79
82
80
52
90
72
85
80
83
72
81
76
dead
dead
94
92
60
73
6
4
3
2
6
3
3
0
1
2
3
1
2
1
0
0
0
2
2
6
1
6
0
3
1
1
3
5
2
3
dead
dead
1
0
1
0
0
1
1
0
0
0
0
0
2
1
1
4
0
0
0
1
0
1
1
0
0
1
0
1
1
1
2
1
1
1
dead
1 dead
0
0
0
0
L>73
-------
SUBCHRONIC TOXKITY OF ORTHO-CRESCL IN SPRAGUE OAWIEY RATS
FEMALE WEMATOLOGY VALUES
[Terminal Sacrifice]
ANIMAL MO,
U3C
SEGS
SANDS
LYMPHS
HONO
EOS
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 rag/kg/day
(x
(x
C*
(x
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3039
3090
3091
3092
3093
3094
3095
3096
3097
3098
3128
3129
3130
3135
3136
3139
9.8
11.7
10.9
5.8
9.6
13.7
11.9
10.8
B.2
12.3
8.3
7,1
13.7
H.I
9.0 •
7.3
10.2
9.6
8,5
8.4
9.9
7.8
10.8
8.0
10.1
7.8
6.9
6.9
10.0
10.4
dead
dead
11.5
10.1
10.4
11.7
0.6
3.6
2.6
0.6
1.6
5.3
1.2
1.1
1.6
0.9
1.3
1.1
1.8-
2.7
1.3
0.9
1.5
1.2
1.1
0.9
1.9
0.9
1.1
1.9
1,1
1.4
0.7
1.5
1.4
2.1
cead
dead
0.6
0.8
4.1
3.2
0.0
0.2
0.2
0.0
0.0
0.0
0.0
0.1
0.1
0.0
0.1
0.2
0.0
0.1
0.0
0.0
0.0
0,0
0.4
0.1
0.0
0.0
0.0
0.0
0.2
0.0
0.1
0.0
0.2
0.0
dead
cead
0.0
0.0
0.0
0.0
3.6
7.3
7.6
5.0
7.4
7.9
10.4
9.6
6.2
11.1
6.6
5.4
11.6
11.1
7.7
6.3
8,7
8.1
6.7
6.9
7,9
6.4
9.7 •
5.8
8,6
6.2
5.7
5.0
8.1
7.9
dead
dead
10.8
9.3
6.2
8.5
0.6
0.5
0.3
0.1
0.6
0.4
0.4
0.0
0.1
0.2
0.2
0.1
0.3
0.1
0.0
0.0
0.0
0.2
0.2
0.5
0.1
0.5
0.0
0.2
0.1
0.1
0.2
0.3
0.2
0.3
•dead
dead
0.1
0.0
0.1
0.0
0.0
0.1
0.1
0.0
0.0
0.0
o.o
0.0
0.2
0.1
0.1
0.3
0.0
0.0
0.0
0.1-
O.D
0.1
0.1
0.0
0,0
0,1
0.0
0.1
0.1
0.1
0,1
0.1
0.1
0.1
dead
dead
0.0
0.0
0.0
0.0
L>74
-------
SUBCBRONtC TOXIC1TY OF ORTHO-CRESOL IN SPRAGUE DAWIEY RATS
MALE CLINICAL CHEMISTRY VALUES
[Interim Sacri fice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
ANIMAL NO.
2881
2882
2883
2884
2885
2886
2337
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
29S4
, 2985
2986
2987
2988
2989
GLU
(mg/dl)
132.0
188.9
202.6
211.7
137.0
188.5
184.0
127.6
179.0
102.9
167.3
141.1
144.1
211.3
149.0
149,8
226.3
154,1
285.0
200.9
310.0
213.4
176.7
238.3
157.8
198.8
179.2
279.4
226.3
177.9
215.3
160,0
373.2
112.8
dead
193.9
214.8
212.0
217.8
189.1
BUN
(mg/dl)
11.0
14.2
18.7
7.9
11.1
13.9
12.6
9.1
13.8
12.4
12.6
15.1
12.8
15.6
9.7
11.3
12.4
13.2
17.9
17.3
14.9
15.4
16.6
12,3
16,4
18,8
17.5
11.9
16.1
17.0
16.1
18.5
13,2
16.4
dead
13.8
9.7
19.1
15.3
16.5
• SGPT
(lu/l)
31
40
42
25
27
41
28
37
35
40
37
32
42
41
33
25
23
28
34
40
47
31
30
32
29
46
40
45
43
37
33
27
67
34
dead
38
35
62
24
86
SGOT
Uu/l)
77
87
66
66
82
70
69
87
78
86
67
82
68
76
82
56
67
66
80
80
72
73
77
72
66
81
76
66
70
81
82
75
98
75
dead
73
79
65
68
94
T PRO
Cg/dl>
6.9
6,8
6.4
6.6
6.7
6,7
7.7
7.0
6.3
5.8
6.8
6.7
6.7
5.9
6.5
6.5
6.3
6.8
6.6
6.0
6.1
7.1
6.6
6.9
7,0
6.8
6.5
6.8
6.3
6.1
6.7
6.3
7.0
6.3
dead
6.4
, 6.7
5.9
7.0
6.5
ALB
(g/dt>
4,0
4.2
3.8
3.6
3.7
3.7
4.1
4.0
3.8
3.5
3.8
3.8
3.5
3.4
3.8
3.7
3.8
3.7
3.9
3.3
3.7
3.9
4.0
4.0
4.0
3.8
3.8
3.8
3.5
3,5
4.0
3.6
4.0
3.7
dead
3.7
3.9
3.7
3.9
3.9
GLOB
(9/dl)
2,9
2,6
2.6
3.0
3.0
3.0
3.6
3.0
2.5
2,3
3.0
2.9
3.2
2.5
2.7
2.8
2,5
3.1
2.7
2.7
2.4
3.2
2.6
2.9
3.0
3.0
2.7
3.0
2.8
2,6
2.7
2.7
3.0
2.6
dead
2.7
2.8
2.2
3,1
2.6
ALB/GIQ8
(ratio)
1,379
1,615
1.462
1,200
1.233
1.233
1.139
1.333
1.520
1.522
1.267
1.310
1.P94
1.360
1.407
1.321
1.520
1.194
1.444
1.222
1.542
1.219
1.536
1.379
1.333
1.267
1.407
1.267
1.250 •
1.346
1.481
1.333
1.333
1.423
dead
1,370
1.393
1.682
1.258
1.500
DKOL
(mg/dl)
63.1
50,6
72.4
85.3
S3.0
83.6
84.6
63,7
63.6
50.4
69.2
52.6
66.4
58.5
70.1
73.9
55,2
89.3
56.4
61.7
47.9
83.3
40. 0
68.9
44.7
65.8
65.2
62.7
42,1
68.5
83.3
56.4
61.7
89.3
dead
58.4
77.5
66.9
87.2
57.6
D-75
-------
SUaCHROMIC TOXSC1TY OF ORTHC-CRESOL IN SPfUGUE DAWLEY RATS
MALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
DOSS LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
.600 mg/kg/day
ANIMAL NO.
2881
2882
2883
28S4
2885
2886
2837
2888
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922 '
2923
2947
2943
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2984
2985
2986
2987
2988
2989
D 8IL
Cmg/dl)
0.00
0.02
0.03
0,02
0.02
0.03
0.00
0.01
0.04
0.01
0,03
C.04
0.01
0.03
0.02
0.01
0.02
0.02
0.01
0.01
0.02
0.02
0.02
0.01
0.01
0.04
0.03
0.02
0.01
0.00
0,02 .
0.01
0.02
0.02
dead
0.03
0.03
0,02
0.01
0.01
T 311
Cmg/dl)
0.18
0.24
0.16
0.16
0.14
0.16
0.11
0.13
0.17
0.10
0.14
0.20
0.14
0.22
0,22
0.15
0.12
0.16
0.10
0.14
0.08
0.11
0.17
0.16
0.15
0.22
0.21
0.13
0.09
0.13
0.19
0.09
0.13
0.17
dead
0.13
0.20
0.17
0.15
0.20
Ca
Cmg/dl >
12.0
13.1
14.2
12.4
10.3
14.4
11.9
11.5
13.6
11.1
11.0 '
11.6
12.3
13.4
11.4
11.5
13.8
11.4
14.8
14.8
13.3
11.9
10.7 -
12.5
10.5
14.2
14.2
14.4
15.0
14.0
11.3
12.0
14.8
11.3
dead
12,8
12.3
12.9
11.6
12.4
Ha
(Heq/L)
143
139
157
145
144
141
144
146
145
141
141
146
139
146
141
142
142
144
158
152
154
185
142
143
141
160
142
143
143
164
143
144
150
144
dead
158
145
153
144
133
K
(Meq/D
7.0
6.9
10.7
6.8
6.2
9.3
6.9
8.7
8.5
7.6
7.1
11.2
6.1
8.3
6,1
7.1
5.9
7.6
9.5
8,0
8.1
5.3
6.7
6.8
6.6
7.8
6,7
5.8
7.4
10.9
7.1
10.5
12.3
6.7
dead
6.6
6.5
8.6
5.5
7.6
Ct
(Heq/U
98
94
110
103
101
98
101
101
101
101
99
102
96
102
97
100
98
102
111
107
108
102
98
100
98
114 •
94
97
96
118
99
104
104
102
dead
112
99
108
98
89
AU PHCS
CIu/l)
94
145
225
106
110
182
98
113
233
106
73
90
92
276
51
64
161
71
260
127
250
56
70
61
102
259
239
123
155
201
87
60
96
79
dead
146
64
171
83
306
C02
(Meq/l)
25
29
21
29
28
21
25
29
24
25
29
25
27
18
27
27
23
21
25
22
19
31
30
25
29
26
22
25
ia
23
25
24
11
27
dead
24
28
23
27
23
GREAT
0.83
0.80
0.62
0.69
0.74
0.63
0.75
0.72
0.66
0.70
0,69
0.88
0.82
0,64
0.82
0.67
0.67
0.64
0.73
0.80
0.62
0.80
0.73
0.76
0.77
C.69
0.70
0.62
0.70
0.58
0.86
0.66
0.68
0.74
dead
0.65 .
-0.76
0.71
0.71
0.66
PHCS
Lrcs/di
10'. 4
9.5
11.5
11.3
10.5
11,1
11.3
10.6
11.4
10.2
9.5
11.7
9,4
9.2
9.5
8.3
9.8
13.3
11.7
11.1
10.8
9.7
10.1
11.0
9.9
1Z.1
10.1
10.8
9.8
12.2
10.3
13.0
12.4
10,1
dead
9.8
10.3
11.5
9.0
9.7
D-76
-------
SU8CHRQNIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWliY RATS
MALI CLINICAL CHEHISTRY VALUES
[Terminal Sacrifice]
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
AH [HAL NO.
2S91
2892
2393
2894
2895
2896
2897
2898
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2994
2996
2998
2999
3001
3003
3005
3007
. GLU
(mg/dl)
365.2
225.9
195.7
242.7
196.0
228.2
212.0
268.5
154.2
279.8
314,1
196.0
173.1
222.1
261.6
341,2
190.3
198.9
167.5
197.4
292.2
240.9
242. 7
272.3
205.8
215.5
260.4
277.1
197.6
278.2
157.1
244.6
151.9
156.1
209.6
201.1
125.0
170.9
260.5
197.8
BUN
(mg/dl 5
18.2
15.4
15.5
14.1
11.9
13.5
15.9
10.6
14.0
13.8
11.8
16.7
11.4
10.8
16.7
14.8
9.4
10.4
12.8
11.6
10.1
13.5
15.3 .
14.9
17. 0_
12.3
15.3
13.9
11.6
14.1
14.1
19.2
11.4
14.0
13.1
11.5
12.3
17.3
15.8
12.5
SGPT
Clu/l)
26
70
29
29
34
25
39
28
489
30
22
28
37
30
111
30
25
29
17
23
23
81
60
32
34
23
28
16
30
65
35
24
27
597
31
36
33
27
20
46
SCOT
Uu/l)
86
97
68
60
77
69
91
83
587
82
49
86
92
52
240
76
62
75
60
63
72
140
93
79
94
60
76
55
85
101
86
64
55
716
75
73
76
86
54
85
T PRO
(S/dl)
7.4
6.2
7.0
6.4
6.7
6.7
6.8
5.2
7.2
7.4
7.2
6.6
5.9
6.6
7.1
7.7
5.1
5.3
5.4
4.9
6.9
7.0
6.1
6.3
6.5
6.9
7.0
6.4
7.5
6.8
6.8
6.0
6.3
7.9
6.1
5.3
6.Z
6.4
5.7
6.5
ALB
(g/di)
4.1
3.5
3.8
3.5
3.8
3.7
3.8
3.1
4.0
3.9
4.0
3.6
3.9
3.5
3.8
4.0
3.2
4.0
4.1
3.5
3.9
4.1
3.5
3.4
3.5
3.8
3.8
3.5
3.8
4.0
3.5
3.2
3.5
4.1
3.5
3.3
3.6
3.9
3.6
3.7
GLOB
(g/dl)
3.3
2.7
3.2
2.9
2.9
3,0
3.0
2.1
3.2
3.5
3.2
3.0
2.0
3.1
3.3
3.7
1.9
1.3
1.3
1.4
3,0
2.9
2.6
2.9
3.0
3.1
3.2
2.9
3.7
2.8
3.3
2.8
2.8
3,8
2.6
2.0
2.6
2.5
2.1
2.8
ALB/GLOB
(ratio)
1.242
1.296
1.188
1.207
1.310
1.233
1.267
1.476
1.250'
1.114
1.250
1.200
1.950
1.129
1.152
1.081
1.684
3.077
3.154
2.500
1.300
1.414
1.346
1.172
1.167
1.226
1.188
1.207
1.027
1.429
1.061
1.143
1.250
1.079
1.346
1.650
1.385
1.560
1.714
1.321
CHOL
(mg/dl)
81.5
42.8
78.8
94.3
138. 7
84.9
85.1
77.9
66.0
76.9
52.5
91.2
56.9
90.0
50.2
97.6
75.2
67.9
63.9
62.8
61.2
95.8
54.0
69.4
81.0
69.0
69.4
53.0
63.5
76.1
73.1
121.5
60.3
128.2
69.1
101.7
79.8
92.1
57,0
47.4
D-77
-------
SU8CHMNIC TOX1C1TY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
HALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice]
DOSE LEVEL
AN1MAI/NQ. D BIU T Bit Ca Na K Cl ALK PHOS C03 CREAT PHOS
(mg/dl) (mg/dl) {mg/dl>
-------
SUBCHRONIC TOXIC1TY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
DOSE LEVEL
0 mg/kg/day
ANIMAL-NO. GLU BUN SGPT SCOT T PRO ALB' GLOB ALB/GLOB CHOL
Cmg/dU (mg/dl) (Iu/l) (Iu/l)
-------
SUBCHRGNIC TOXICITY OF ORTHQ-CRESQL IN SPRAGUE DAULEY RATS
FEMALE CLINICAL CHEMISTRY VALUES
[Interim Sacrifice]
DOSE LEVEL
0 mg/kg/day
SO mg/kg/day
175 mg/kg/day
600 mg/kg/day
AN I HAL NO.
3013
30H
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3112
3113
3114
3115
3116
3117
3118
3119
3120
3121
0 B1L
Cmg/dl)
0.02
0.00 .
0.01
0,01
0.01
0.02
0.04
0.01
0.01
0.02
0.07
0.01
0.03
0.03
0.02
0.01
0.02
0.02
0.00
0.02
0.02
0.01
0.08
0.02
0.02
0.00
0.01
0.01
0.02
0.04
dead
dead
0.00
0,04
0.00
0.01
0.01
0.01
0.01
dead
T BIL
(mg/dl)
0.17
0.13
0.15
0.11
0.11
0.11
0.20
0.07
0.22
0.14
0.21
0.14
0.20
0.18
0.12
0.14
0.10
0.19
0.10
0.12
0.15
0.13
0.17
0.18
0.15
0.22
0.08
0.14
0.15
0.17
dead
dead
0.15
0.24
0.17
0.17
0.21
0.16
0.13
dead
Ca
Crog/dl3
14.0
15.2
12.4
15.0
12.0
14.8
,13.6
14.0
15.1
U.O
12.5
12.8
17.0
11.9
12.8
13.3
12.2
10.8
11.7
13.3
13.7
11.7
13.5
12.6
13.0
12.3
12.3
15.2
12.7
14.3
dead
dead
12.4
13.1
14.8
11.8
13.2
12.9
15.4
dead
Na
(Meq/l)
145
139
146
145
143
155
141
141
154
164
150
157
147
140
143
162
146
188
145
150
142
191
144
144
183
142
142
145
176
147
dead
dead
144
151
141
141
1*3
143
145
dead
<
(Meq/O
7.5
7.8
10.4
7.8
6.4
10.0
9.1
9.1
7.6
13.4
8.5
7.7
9.4
7.8
6.9
8.4
7.7
10.9
8.1
8.3
8.3
9.9
8.0
8.0
10.1
7.0
7.8
10.1
9.1
7.9
dead
dead
9.5
9.7
7.7
7.0
9.5
9.0
6.9
dead
Cl
(Meq/l)
ICO
97
107
100
100
110
99
98
111
123
102
108
101
99
100
117
101
145
103
103
97
148
100
100
136
100
101
103
129
104
dead
dead
100
109
99
95
101
101
99
dead
ALK ?HOS
ciu/n
97
90
127
85
72
59
143
120
60
76
87
88
364
141
88
108
38
50
58
88
66
116
216
96
46
43
110
89
98
159
dead
dead
82
117
134
46
122 '
92
65
dead
C02
(Meq/l)
20
21
20
29
26
19
20
20
22
20
24
19
20
20
25
21
22
26
26
23
23
24
19
19
24
24
23
12
18
22
dead
dead
20
18
19
28
21
20
17
dead
GREAT
(mg/dl)
0.67
0.62
0.80
0.62
0.71
0.72
0.62
0.59
0.66
0.66
0.75
0.72
0.67
0.77
0.72
0.52
0.73
0.67
0.69
0.65
0.69
0.72
0.75
0.56
0.68
0.89
0.77
0.66
0.72
0.76
dead
dead
0.86
0.69
0.67
0.83
0.70
0.86
0.66
dead
PHOS
(mg/d'l)
9.6
9.9
10.9
10.6
8.1
10.8
10.2
10.9
9.9
11.0
9.4
9.6
11.9
9.4
' 8.5
10.3
8.5
8.8
8.2
11.0
9.7
9.3
10.1
9.4
10.1
9.6
9.2
12.0
9.7
10.6
dead
dead
10.1
10,4
10.0
9.1
9.2
9.6
8.8
dead
D-80
-------
SU8CH8QN1C TOXIC ITY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEHALE CLINICAL CHEMISTRY VALUES
[Terminal Sacrifice!
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
AMIMAL MO.
3023
3024
3025
3026
3027
3023
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3130
3135
3136
3139
GLU
(mg/dl)
137.7
151.5
155.4
160.6
198.2
202.1
298.8
162.2
147.7
156.3
206.0
163.2
204.5
158.0
142.7
288.7
202.3
219.6
128.1
140.1
186.8
182.3
162.4
264.2
204.9
169.0
106.4
210.4
243.4
205.0
168.2
124.6
148.8
158.7
SUN
(mg/dt)
13.0
16.0
15.0
14.3
16.2
16.0
13.7
13.5
12.6
15.8
14.4
10.7
14.7
9.1
20.3
11.6
15.1
12.5
12.8
10.6
19.5
13.2
19.7
13.7
18.0
11.2
19.7 '
14.2
14.0
14.3
20.4
15.5
15.0
14.6
SGPT
(lu/U
27
18
27
22
31
22
25
18
26
26
21
17
74
31
28
36
44
25
25
21
21
28
28
43
B5
27
32
80
25
27
46
24
27
23
SGOT
Uu/l)
77
65
82
55
103
55
81
81
83
68
85
- 71
'153
74
65
97
101
71
81
66
46
89
65
85
150
93
82
176
69
77
89
65
121
56
T ?m
(g/du
7.2
6.3
6.8
6.7
7.1
7.5
a.3
6.2
5.1
6.3
7.6
5.3
6.6
6.1
6.8
8.0
7.8
7.2
6.2
6.4
7.2
7.1
7.6
8.9
7.2
7.5
6.4
8.1
6.8
7.3
7.2
6.2
7.6
6.2
ALB
(g/dl)
4,5
4.0
4.0
4.4
"4.1
4.7
4.7
3.8
4.1
3.7
4,5
4.6
4.2
3.9
3.9
4.6
4.5
4.7
4.5
4.2
4.1
4.4
4.6
5.3
4.6
4.3
3.9
4.5
3.9
4.4
4.6
4.0
4.2
3.7
GLOB
Ca/di)
2.7
2.3
2.8
2.3
3.0
2.8
3.6
2.4
1.0
2.6
3.1
0.7
2.4
2.2
2.9
3.4
3.3
2.5
1.7
2.2
3.1
2.7
3.0
3.6
2.6
3.2
2.5
3.6
2.9
2.9
2.6
2.2
3.4
2.5
ALB/GLOB
(ratio)
1.667
1.739
1.429
1.913
1.367
1.679
1.306
1.583
4,100
1.423
1.452
6.571
1.750
1.773
1.345
1.353
1,364
1.SSO
2.647
1.909
1.323
1.630
1.533
1.472
1.769
1.344
1.560
1.250
1.345
1.517
1.769
1.818
1,235
1.480
CHOL
(mg/dl)
70.4
71.9
94.8
106.4
63.9
123.6
63.3
112.7
100.8
89.5
88.5
74.9
121,1
72.4
86.3
105.3
38.6
48.7
80.9
69.0
62.9
103.3
B6.8
119.8
129.0
118.7
65.4
129.8
61.2
86. 3
89.8
90.3
121,4
95.0
D-81
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWUEY RATS
FEMALE CLINICAL CHiMISTRY VALUES
{Terminal Sacrifice]
ANIMAL 'NO.
DOSE LEVEL
0 mg/kg/day 3023
3024
3025
3026
3027
302S
3029
3030
3031
3032
50 ing/kg/day 3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
175 mg/kg/day 3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
600 mg/kg/day 3130
3135
3136
. . 3139 .
D B!L
(mg/dl)
0.00
0.00
0.02
0.00
0.02
0.01
0.02
0.01
0.00
0.02
0.02
0.00
0.02
o.do
0.01
0.02
0.01
0.01
0.00
0.00
0.02
0.01
0.02
0,03
0.02
0.02
0.01
0.02
0.01
0.00
0.02
0.01
O.QO
0.02
T BIL
(mg/dl)
0.19
0.04
0.09
0.10
0.09
0.08
0.06
0.06
0.09
0.06
0.05
0.13
0.09
0.06
0.10
0.05
0.08
0.1V
0.11
0.08
0.01
0.09
0.06
0.10
0.08
0.07
0.12
0.21
0.02
0.12
0.13
0.10
0.04
0.08
CA
(mg/dl)
12.7
12.8
13.9
13.6
13.8
14.1
13.5
12.1
12.3
11.0
13.3
13.7
12.2
12.6
11.8
13.8
12.7
14.8
13.5
13.2
12.8
12.3
14.8
16.0
13.7
13.4
11.5
13.7
11.0
13.1
13.7
12.3
13.0
10.8
Na
(Meq/l)
149
150
153
153
151
154
156
153
146
151
147
154
155
153
152
155
159
148
157
157
159
149
151
158
148
152
150
224
55
149
CHS
153
155
160
K
CMeq/l)
9.5
10.1
11.3
9.6
8.7
8.1
8.4
8.7
9.6
10.3
9.8
8.2
10.6
11.1
12.3
10.1
9.5
a. s
13.2
8.2
8.2
7.6
9.6
15.8
8.9
9.9
11.0
16.5
8.8
10,3
CHS
10.8
10.7
10.5
Ct
(Meq/l)
101
103
101
102
104
100
92
105
104
104
103
95
102
97
101
98
99
104
99
108
96
102
104
95
103
101
106
146
92
101
QMS
104
102
97
ALK PKOS
(lu/l)
30
41
70
51
38
61
55
41
38
58'
30
36
100
30
58
56
24
25
75
61
31
84
49
30
34
42
71
48
50
149
58
34
34
48
C02
(Heq/l)
20
16
24'
21
25
23
18
27
20
24
23
19
25
17
17
22
26
18
13
20
, 22
17
26
19
25
20
19
22
18
23
QMS
25
22
25
GREAT
Crag/dl)
0.95
0.74
0.76
0.73
0.91
0.65
0.74
0.60
- 0.71
0.65
0.75
0.69
0.68
0.64
0.73
0.81
0.77
0.84
0.78
0.65
0.66
0.86
0.76
0.75
0.71
0.74
0.71
0.96
0.74
0.97
0.77
0.66
0.76
0.65
PHOS
(mg/dt.
8.1
9.0
9.3
8.1
10.3
9.5
8.5
12.4
7.1
10.9
9.5
7.0
10.6
7.6
10.7
8.S
9.1
7,6
8.0
7.6
7.5
7.6
10.3
12.1
10,5
10,0
9.6
7.3
8.4
9.5
12.4
12.0
10.6
9.4
QNS = quantity not sufficient to assay.
D-82
-------
SUBCHROMIC TQXICITY OF OSTHO-CRESOL IN SPRAGU'E DAULEY RATS
RELATIVE HALE ORGAN WEIGHT DATA (X Terminal Body Height)
[Terminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KIDNEY-LFT KIDNEY-RT
DOSE LEVEL
0 mg/kg/day
50 rag/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
0.360
0.292
0.335
0.302
0.319
0.334
0.329
0,299
0.366
0.317
0.317
0.300
0.330
0.323
0.297
0.296
0.299
0.312
0.307
0.326
0.350
0.336
0.285
0.314
0.692
0.257
0.368
0.347
0.273
0.363
0.31H
0.313
0.304
0.296
0.306
0.363
0.292
0.264
0.317
0.293
3.520
3.281
3.499
3.099
3.515
3.292
3.313'
3.185
3.158
3.762
3.132
3.256
3.195
3.021
3.038
3.772
3.446
2.983
3.661
3.605
2.837
3.533
3.283
3.244
7.044
2.986
2.877
3.705
3.006
3.890
3.372
3.701
3.278
2.875
3.027
3.032
3.374
2.755
3.389
3.791
0.150
0.143
0.134
0.131
0.111
0.137
0.146
0.138
0.142
0.151
0.153
0.120
0.153
0.136
0.129
0.157
0.143
0.135
0.193
0.129
0.147
0.138
0.132
0.117
0.312
0.112
0.117
0.160
0.131
0.161
0.183
0.145
0.149
0.159
0.123
0.142
0.135
0.133
0.135
0.161
0.375
0.390
0.385
0.349
0.358
0.349
0.339
0.341
0.367
0.429
0.378
0.341
0.343
0.296
0.332
0.431
0.370
0.317
0.392
0.417
0.327
0.405
0.390
0.388
0.841
0.369
0,360
0.381
0.375
0.368
0.357
0.357
0.409
0.315
0.366
0.360
0.356
0.280
0.333
0.330
0.374
0.397
0.379
0.345
0.373
0,372
0.336
0.343
0.375
0.455
0.379
0.326
0,356
0,305
0.355
0.398
0.380
0.335
0.401
0.414
0.329
0.425
0.398
0.408
0.868
0.330
0.393
0.400
0.359
0.367
0.369
0.343
0.437
0.292
0.397
0.383
0.370
0.305
0.381
0.343
D-83
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWL£Y RATS
RELATIVE MALE CRGAM WEIGHT DATA <% Terminal Body yeight)
[Terminal Sacrifice]
ANIMAL NO. TEST1S-LFT TESTIS-RT ADRENALS BRAIK THY./PARA.
DOSE LIVEL
0 mg/kg/day
50 mg/kg/day
2391
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
0.343
0.361
0.339
0.352
0.308
0.320
0.326
0.338
0.342
0.285
0.296
0.234
0.365
0.285
0.295
0.211
0.295
0.309
0.328
0.308
0.358
0.311
0.257
0.352
0.754
0.315
0.124
0.329
0.285
0.253
0.348
0.181
0.331
0.253
0.360
0.35S
0.297
0.282
0,359
0.249
0.350
0.365
0.352
0.337
0.308
0.304
0.315
0.343
0.343
0.284
0.296
0.248
0.353
0.300
0.309
0.315
0.297
0.289
0.328
0.310
0.353
0.314
0.269
0.336
0.783
0.327
0.124
0.331
0.286
0.268
0.348
0.302
0.336
0.244
0.350
0.363
0.294
0.278
0.370
0.220
0.012
0.012
0.010
0.010
0.009
0.010
0.012
0.012
0.012
0.007
0.013
0.010
0.010
O.D10
0.010
0.005
0.009
0.007
0.013
0.009
0.010
0.012
0.011
0.011
0.024
0.012
0.010
0.006
0.010
0.009
0.012
0.010
0.010
0.009
0.008
0.013
0.011
0.007
0.009
0.010
0.419
0.479
0.398
0.438
0,400
0.377
0.375
0.415
0,405
0.360
0.417
0.394
0.408
0.418
0.416
0.410
0.381
0.366
0.420
0.414
0.416
0.399
0.413
0.454
0.815
0.399
0.451
0.384
0.366
0.398
0.446
0.370
0.357
0.380
0.428
0.467
0.371
0.373
0.409
0.357
0.005
0.005
0.007
0.006
0.007
0.004
o:oos
0.005
0.004
0.009
0.005
0.009
0.005
0.008
0.004
0.004
0.006
0.004
0.007
0.004
0.007
0.004
0.008
0.005
0.015
0.009
0.004
0.006
0.005
0.005
0.006
0.004
0.005
0.005
0.006
'0.007
0.002
0.005
0.009
0.003
D-84
-------
SUBCHRONIC TOXJC1TY OF ORTHO-CR1SOL IN SPRAGUE DAWLEY SATS
RELATIVE HALE ORGAN WEIGHT DATA (% Terminal Sody Weight)
[Terminal Sacrifice]
ANIMAL TO. HEART LIVER SPLEEN KIDNEY-LFT
COSE i;EVEL
175 ms/kg/day
600 mg/kg/day
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2963
2969
2970
2971
2972
2973
2974
2975
2976
2990
2991
2994
2996
2998
2999
3001
3002
3003
3005
3007
3009
0.320
0.265
0.366
0.279
0.320
0.325
0.311
0.334
0.347
0.319
0.362
0.333
0.296
0.289
0.324
0.327
0.304
0.293
0.271
0.319
0.313
0.331
0.321
0.322
0.3&6
0.324
0.319
0.330
0.300
0.355
0.307
0.306
3.386
3.145
3.172
3,239
3.533
3.218
3.792
3.378
3.612
3.440
3.219
3.282
3.281
3.360
3.260
3.256
2.907
2.921
2.917
3.981
3.300
3.796
3.904
3.657
3.438
3.189
3.091
3.557
3.086
3.931
3.911
3.427
0.130
0.135
0.131
0.126
0.116
0.141
0.130
0.137
0.157
0.139
0.168
0.144
0.151
0.142
0.146
0.139
0.117
0.155
0.149
0.115
0.120
0.151
0.135
0.148
0.142
0.136
0.148
0.122
0.160
0.147
0.132
0.131
0.366
0.327
0.373
0.373
0.410
0.436
0.454
0.447
0.379
0.378
0.404
0.360
0.356
0.375
0.446
0.388
0.315
0.362
0.360
0.375
0.401
0.430
0.475
0.407
0.464
0.415
0.399
0.412
0.350
0.474
0.403
0.445
0.339
0.341
0.394
0,360
0.385
• 0.386
0.450
0.411
0.400
0.383
0.378
0.380
0.366
0.330
0.465
0.401
0.310
0.373
0.335
0.411
0.377
0.438
0.473
0.418
0.474
0.414
0.429
0.422
0.359
0.490
0.403
0.450
D-85
-------
SUBCHRQNIC TOXICITY OF ORTHO-CRESQL IN SPRAGUE DAWLEY SATS
RELATIVE MALE OR5AW UEEGHT DATA (% Terminal Body Weight)
[Terminal Sacrifice]
ANIMAL NO. TEST1S-LFT TESTSS-RT ADRENALS 8RAIN THY./PARA.
DCSE LEVEL
175 mg/'
-------
SUiCHRONIC TOXiCITY OF OSTHO-CRESQL IN SPRAGU6 DAULEY RATS
RELATIVE FEMALE ORGAN UEIGHT DATA (% Terminal Body Weight)
[Terminal Sacrifice]
ANIMAL NO. HEA8-T LIVES SPLEEN KIDMEY-LFT KIDNEY-RT
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
0.351
0.308
0.324
0.368
0.417
0.341
0.330
0.330
0.346
0.316
0.448
0.347
0.407
0.366
0.364
0.297
0.373
0.361
0.324
0.322
0.400
0.346
0.372
0.360
0.330
0.36S
0.337
0.323
0.380
0.321
0.546
0.341
0.392
0.352
0.329
0.365
0.361
0.350
0.400
0.374
'3.081
2.665
3. 158
3.382
3.349
3.154
3.500
3.409
3.135
2.982
3 .477
3.519
3.011
3.079
3.258
2.745
3,135
3.481
3.346
3.243
3.116
3.064
3.519
3.057
2.801
3.071
2.9S2
3.233
3,416
3.037
3.225
3.030
3.165
3.269
3.225.
2.735
3.092
3.399
3.425
3.106
0.193
0.173
0.175
0.219
0.190
0.183
0.192
0.224
0.195
0.182
0.177
0.217
0.210
0.198
0.139
0.169
0.188
0.187
0.159
0.188
0.156
0.175
0.185
0.170
0.148
0.192
0.159
0.194
0.171
0.153
0.199
0.165
0.184
0.196
0.169
0.183
0.219
0.179
0.207
0.160
0.4CS
0.302
0.309
0.375
0.441
0.369
0.397
0.419
0.366
. 0.338
0.435
0.380
0.443
0.396
0.361
0.338
0.482
0.374
0.372
0.368
0.344
0.391
0.407
0.370
0.347
0.400
0.334
0.419
0.431
0.402
0.427
0.365
0.398
0.380
0.392
0.335
0.374
0.395
0.398
0.340
0.458
0.301
0.304
0.415
0.439
0.366
0.407
0.439
0.389
0.349
0.464
0.395
0.384
0.381
0.399
0.394
0.528
0.361
0.376
0.368
0.353
0.445
0,438
0.354
0.363
0.433
0.359
0.447
0.438
0.378
0.421
0.359
0.409
0.407
0.362
0.345
0.373
0.429
0.421
0.356
r>87
-------
SUBCHRQNiC TOX1C1TY OF ORTHQ-CRESOL !M SPRAGUE DAytEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA {% Terminal Body Weight)
[Terminal Sacrifice]
ANIMAL NO. OVARY-LFT OVARY-HT ADRENALS BRAiM THY./PARA,
DOSE 'LEVEL
0 mg/kg/day 3023
3024
3025
3026
3027
3028 ,
3029
3030
3031
3032
3033
3034
3035
3036
3037
. 3038
3039
3040
3041
3042
50 mg/kg/day 30S6
3057
30S8
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
O.D16
0.018
0.015
0.017
0.037
0.011
0.015
0.017
0.014
0.018
0.014
0.018
0.011
0.014
0.013
0.010
0.023
0.018
0.010
0.016
na
0.016
0.014
0.013
0.019
0.023
0.008
0.003
0.014
0.014
0.018
0.012
0.012
0.016
0.013
0.008
0.017
0.019
0.021
0.014
0.017
0.011
0.016
0.020
0.032
0.012
0.017
0.016
0.018
0.011
0.019
0.018
0.012
0.021
0.016
0.009
0.016
0.019
0.006
0.018
na
0.012
0.012
0.013
0.018
0.022
na
0.007
0.016
0.012
0.020
0.014
0.017
0.015
0.007
0.017
0.013
0.018
0,021
0.014
0.030
0.021
0.019
0.023
0.024
0.023
0.024
0.021
0.020
Q.Q25
0.022
0.033
0.019
0.021
0.029
0.022
0.030
0.024
0.020
0.030
0.027
0.026
0.020
0.021
0.032
0.026
0.015
0.022
0.027
0.016
0.023
0.024
0.019
0.025
0.018
0.016
0.023
0.026
0.022
0.014
0.789
0.710
0.679
0.793
0.748
0.699
0.752
0.800
0.738
0.730
0.807
0.815
0.783
0.780
0.766
0.740
0.739
0.812
0.731
0.829
na
0.694
0.659
0.695
0.766
0.668
0.702
0.678
0.349
0,616
0.780
0.629
0.752
0.677
0.631
0.612
0.691
0.828
0.756
0.582
0.014
0.008
0.011
0.010
0.007
0.008
0.010
0.009
0.008
0.005
0.011
0.006
0.007
0.013
0.006
0.012
0.012
0.010
0.011
0.012
0.007
0.008
0.007
0.008
0.006
0.008
0.008
0.012
0.009
0.011
0.010
0.008
0.010
0.010
0.006
0.006
0.008
0.007
0.006
0.009
na = no data available.
D-88
-------
SUBCHRON1C TOXICITY OF ORTHO-CSESOL IN SPRAGUE DAUIEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA (X Terminal Body Weight)
[Terminal Sacrifice]
ANIMAL SO. HfART LIVER SPIEEN KIONEY-LFT KIONET-RT
DOSS LEVEL
175 mg/kg/day
600 mg/kg/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
310!
3102
3103
3104
3105
3106
3107
3108
3130
3135
3136
3139
0.376
0.400
0.328
0.452
'0.396
0.344
0.340
0.310
0.399
0.342
0.324
0.314
0.346
0.372
0.343
0.335
0.317
0.364
0.403
0.336
0.363
0.308
0.362
0.397
3.184
3.265
3.083
4.023
3.350
3.451
3.414
2.965
3.145
3.285
3.344
3.081
2.854
3.123
3.122
3.363
3.034
2.850
3.290
3.106
3.191
3.293
3.215
3.577
0.223
0.206
0.220
0.160
0.201
0,187
0.188
0,202
0.245
0.216
0.196
0.173
0.232
0.181
0.166
0.177
0.191
0.186
0.169
0.159
0.211
0.207
0.153
0.245
0.391
0.462
0.403
0.474
0.411
0.332
0.415
0,351
0.454
0.334
0.392
0.350
0.307
0.39Q
0.463
0.356
0.329
0.370
0.426
0.388
0.377
0.387
0.363
0.421
0.412
0.471
0.422
0.500
0.432
0.338
0.427
0.374
0.485
0.377
0.397
0.367
0.308
0.613
0.416
0.402
0.332
0.363
0.420
0.398
0.390
0.418
0.385
0.409
D-89
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
RELATIVE FEMALE ORGAN WEIGHT DATA C%.Terminal Body Weight)
[Terminal Sacrifice]
ANIKAL NO. OVARY-LFT OVARY-RT ADRENALS ERAJN IKY./PARA,
DOSE LEVEL
175 mg/kg/day
600 mg/kg/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
3130
3135
3136
3139
0.013
0.012
0.01S
0.017
0.016
0.018
0.017
0.032
0.013
0.014
0.016
0.015
0.018
0.013
0.016
0.011
0.011
0.011
0.019
0.021
0.026
0.017
0.017
0.016
0.019
0.011
0.01S
0.018
0.016
0.020
0.019
0.028
0.018
0.019
0.018
0.011
0.016
0.021
0.014
0.008
0.013
0.013
0.017
0.014
0.02T
0.009
0.014
0.011
0.023
0.024
0.020
0.025
0.024
0.023
0.025
0.029
0.024
0.026
0.015
0.012
0.024
0.024
0.028
0.014
0.022
0.019
0.034
0.023
0.025
0.029
0.029
0.026
0.769
0.897
0.838
0.709
0.720
0.628
0.762
0.784
0.725
0.793
0.282
0.625
0.662
na
0.835
0.662
0.630
0.776
0.833
0.756
0.820
0.831
0.797
0.754
0.011
0.015
0.011
0.008
0.012
0.008
0.010
0,008
0,012
0.010
0.008
0.008
0.007
0.005
0.012
0.003
0.009
0.012
0.009
0.011
0.013
0.009
0.009
0.012
D-90
-------
SUiCHRONIC TOXICITY OF QRTHQ-CRESOL IN SPRAGUE DAULEY RATS
MALE ORGAN WEIGHT DATA
-------
SUBCHRON1C TOX1CITY OF ORTHO-CRESOL IN SPRAGUE DAULET RATS
MALE ORGAN WEIGHT DATA (g)
[Terminal Sacrifice]
ANIMAL NO. TESTIS-LFT TESTIS-RT ADREKALS BRAIN THY./PARA. TERM. UGT,
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901
2902
2903
2904
2905
2906
2907
2908
2909
2910 •
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
1.827
1.599
1.720
1.723
1.566
1.752
1.827
1.876
1,656
1.712
1.620
1.272
1.918
1,533
1.560
1.090
1.717
1.706
1.667
1.493
1.902
1.787
1.348
1.707
1.929
1.698
0.563
1.783
1.601
1.364
1.665
1.108
1.995
1.337
1,816
1.806
1.674
1.665
1.980
1.478
1.862
1.618
1.783
1.653
1.570
1.667
1.765
1.906
1.661
1.703
1.624
1.349
1.S57
1.613
1.633
1.624
1.730
1.598
1.668
1.500
1.879
1.804
1.412
1.632
2.0C5
1.761
0.562
.795
.606
.444
.663
.848
2.029
1.290
1.766
1.827
1.658
1.645
2.043
1.305
0/063
0.053
0.051
0.048
0.047
0.054
0.068
0.064
0.059
0.040
0.071
0.053
0.050
0.055
0.051
0.027
0.055
0.041
0.066
0.045
0.055
0.068
0.060
0.054
0.062
0.062
0.044
0.034
0.055
0.048
0.056
0.060
0,061
0.045
0.041
0.067
0.064
0.044
0.049
0.058
2.227
2.124
2.016
2.148
2.038
2.067
2.101
2.301
1.960
2.157
2.285
2.138
2.146
2.246
2.194
2.117
2.222
2.020
2.136
2.006
2.214
2.293
2.164
2.202
2.086
2.148
2.044
2.082
2.055
2.143
2,131
2.267
2.151
2.008
2.159
2.352
2.092
2.206
2.260
2.118
0.027
0.023
0.034
0.028
0.034
0.024
0.026
0.027
0.017
0.052
0.028
0.050
0.026
0.044
0.022
0.022
0.033
0.021
0.036
0.019
0.037
0.025
0.040
0.026
0.038
0.051
0.018
0.031
0.026
0.026
0.031
0.024
0.032
0.024
0,028
0.034
0.014
0.027
0.048
0.020
532
443
507
490
509
548
560
555
484
600
548
543
526
537
528
516
583
552
508
454
532
575
524
485
256
539
453
542
561
539
478
612
603
529
505
504
564
591
552
594
D-92
-------
SUBCHROH1C TOXICITY OF QRTHQ-CRESOL IN SPRAGUE DAULEY RATS
MALE ORGAN HEIGHT DATA (g)
tTerminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KSDNEY-LFT KIDNEY-RT
DOSE LEVEL
175 mg/kg/day
600 mg/kg/day
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
299Q
2991
2994
2996
2998
2999
3001
3002
. 3003
3005
3007
3009
1.714
1.591
1.735
1.616
1.748
1.732
1.932
1.761
1.897
1.568
1.902
1.836
1.702
1.795
1.583
2.018
1.837
1.483
1.317
1,533
1.636
1.650
1.797
1.370
1.835
1.377
1.495
1.760
1.532
1.750
1.560
1.373
18.148
18.872
15.227
18.786
19.327
17.150
23.550
17.834
19.719
16.890
16.900
18.115
18.866
20.366
15.908
20.087
17.585
14.807
14.177
19.111
17.257
18.904
21 .863
15.542
17.260
13.554
14.464
18.994
15.740
19.379
19.869
15.388
0.697
0.811
0.627
0.733
0.637
0.751
0.803
0.722
0.859
0.683
0.881
0.795
0.870
0.884
0.711
0.860
0,709
0.785
0.723
0.551
0.628
0.751
0.756
0.627
0,713
0.578
0.691
0.649
0.814
0.725
0.671
0.588
1.962
1.959
1.792
2.162
2.241
2.325
2.818
2.362
2.067
1.858
2,119
1.985
2,047
2.326
2.177
2.391
1.903
1.834
1.749
1.802
2.095
2.140
2.661
1.730
2.327
1.763
1.869
2.202
1.787
2.339
2.049
2.000
1.818
2.047
1.891
2.089
2.105
2.057
2.792
2.172
2.186
1.830
1.984
2.096
2.104
2.360
2.267
2.476
1.875
1.893
1.626
1.973
1.972
2.182
2.646
1.778
2.378
1.761
2.010
2.251
1.831
2.415
2.045
2.019
D-93
-------
SU8CHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE OAyLEY RATS
• MALE ORGAM UEIGHT DATA
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEHALE ORGAN WEIGHT DATA (g)
[Terminal Sacrifice]
ANIMAL NO. HEART LIVER SPLEEN KIONEY-LFT KIDNEY-RT
DOSE LEVEL
0 mg/kg/day
50 rag/kg/day
3023
3024
3025
3026
3027
3028
3029
3030
3Q31
3032
3033
3034 '"
3035
3036
3037
3038
3039
3040
3041
3042
305
-------
SUBCHRONIC TOXICITY OF ORTKO-CRESOL IN SPRAGUE CAWLEY RATS
FEMALE ORGAM WEIGHT DATA (g)
[Terminal Sacrifice!
ANIMAL NO. OVARY-LFT QVARY-RT ADRENALS BRAIN THf./PARA. TERM. WOT.
DOSE LEVEL
0 mg/kg/day 3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
50 mg/kg/day . 3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3066
3067
3068
3069
3070
3071
3072
3073
3074
3075
0.040
0.047
0.046
0.042
0.108
0.028
0.040
0.042
0,033
0.046
0.037
0,045
0.023
0,035
• 0.033
0.026
0,060
0.045
0.025
0.037
na
0.050
0.046
0.037
0.045
0.067
0.024
0.009
0.036
0.045
0.048
0.038
0.028
0.050
0.038
0.024
0.046
0.048
0.056
0.041
0.042
0.030
0.050
0.048
0.092
0.033
0.045
0.040
0.047
0.028
0.048
0.046
0.029
0.053
0.040
0.023
0.041
0.048
0.017
0.042
na
0.038
0.039
0.036
0.042
0.064
na
0.020
0.041
0.040
0.055
0.044
0.041
0.046
0.022
0.050
0.036
0.046
0.055
0.041
0.072
0.056
0.059
0.057
0.071
0.062
0.062
0.051
0.054
0.063
0.056
0.083
0.046
0.053
0.072
0.059
O.Q78
0.060
0.052
Q.Q70
0.069
0.081
0.063
0.059
0.075
0.075
0.044
0.060
0.068
0.051
0.063
0.074
0.046
0.076
0.055
0.047
0.063
0.065
0.060
0.043
1.924
1.860
2.085
1.955
2.168
1.852
1.947
1.960
1.955
1.876
2.083
2,070
1.918
1.965
1.923
1.977
1.935
2.062
•1.915
1.940
na
2.193
2.130
1.940
1.7B5
1.995
2.128
1.851
0.872
2.022
2.130
1.951
1.790
2.099
1.887
1.836
1.893
2.061
2.027
1.764
0.035
0.020
0.035
0.024
0.019
0.020
0.026
0,021
0.021
0.013
0.029
0.015
0.017
0.034
0.015
0.032
0.032
0.026
0.030
0.027
0.017
0.024
0.021
0.022
0.014
0.023
0.025
0.034
0.022
0.036
0.026
0.025
0.024
0.032
0.019
0.017
0.021
0.017
0.017
0.027
244
262
307
245
290
265
259
245
265
257
258
254
245
252
251
267
262
254
262
234
255
316
323
279
233
290
303
273
250
328
273
310
238
310
299
300
274
249
268
303
na = no data available,
D-96
-------
SUiCHRQNIC TOX5CITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEHAli ORGAN WEIGHT DATA (g)
[Terminal Sacrifice]
ANLHAL NO. HEART LIVER SPLiEN KtDNEY-LFT K10NEY-RT
DOSE LEVEL
175 mg/kg/day
600 mg/ks/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
309S
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
3130
3135
3136
3139
0.985
0.915
0.804
1.315
1.117
0.976
0.802
0.785
0.985
0. 814
0.940
0.968
0.984
1.037
0.874
0.984
0.929
0.968
0.924
0.934
0.879
0.714
0.383
1.017
8.341
7.476
7.554
11.721
9.448
9.802
8.057
7,. 501
7.767
7.818
9,697
9. 488
8.104
B.713
7.962
9.886
8.890
7.662
7.534
8.636
7.626
7.639
7.845
9.157
0.585
0.472
0.540
0.465
0.566
0.532
0.444
0.510
0.604
0.515
0.568
0.547
0.658
0.505
0.423
0.519
0.361
0.496
0.388
0.442
0.505
0.480
0.374
0.628
1.025
1.059
0.987
1.378
1.1S9
0.942'
0.980
0.888
1.121
0.795
1.136
1.078
0.871
1.087
1.181
1.048 -
0.965
0.985
0.975
1.080
0.901
0.897
0.898
1.079
1.079
1.078
1 .034
1.455
1.219
0.961
1.008
0.946
1.199
0.898
1.150
1.129
0.876
1.710
1.062
1.181
0.973
0.965
0.962
1.106
0.931
0.970
0.939
1.046
D-
97
-------
SUBCHRONIC TOXtCITY OF ORTHO-CRESOl JN SPRAGUE DAULEY RATS
fEMALE ORGAN UEIGHT DATA
[Terminal Sacrifice!
ANIMAL NO, QVARY-LFT OVARY-RT ADRENALS BRAIN THY./PARA.
fERH, WGT.
DOSE IEVEC
175 mg/kg/day
600 mg/kg/day
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
310S
3106
3107
3108
3130 .
3135
3136
3139
0.034
0.027
Q.Q44
0.050
0.044
0.050
0.039
0.080
0.033
0.034
0.047
0.045
0.052
0.037
0.041
0.031
0.032
0.030
0.044
0.057
0.063
0.039
0.042
0.040
0,050
0.025
0.043
0.052
0.044
0.057
0.044
0.072
0.045
0.046
0.051
0.034
0.045
0.059
0.036
0.024
0.039
0.035
0.040
0.038
0.049
0.022
0.034
0.027
0.059
0.055
0.050
0.074
0.068
0.065
0.058
0.074
0.060
0.062
0.043
0.037
0.067
0.066
0.072
0.042
0.064
0.050
0.078
0.063
0.060
0.068
0.071
0.066
2.014
2.053
2.053
2.063
2.030
1.7S4
1.798
1.9S4
1.790
1.888
0.818
1.924
1.879
na
2.128
1.945
• 1.847
2.064
1.907
2.103
1.960
1.928
1.945
1.931
0.030
0.035
0.026
0.022
0.035
0.022
0.024
0.019
0.030
0.024
0.023
0.026
0.021
0.015
0.030
0.010
0.027
0.032
0.021
0.031
0.030
0.021
0.021
0.031
262
229
245
291
282
284
236
253
247
238
290
308
284
279
255
294
293
266
229
278
239
232
244
256
D-98
-------
SUBCHRON1C TOXIC1TY OF ORTHO-CRESOL IN SPRAfiUE DAULEY RATS
MALE URINALYS1S DATA
[Interim Sacrifice!
Animal no. App. Vol. (ml) Sp. Gr. Color pH Protein Glucose Ketones Uro. Situ Stood Hgb.
DOSE LEVEL
0. mg/ kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2881
2832
2883
2834
2885
2886
2887
2838
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2980
2981
2982
2983
2985
2986
2987
2988
2989
cl
cl
cl
cl
hz
cl
el
c
cl
hz
cl
cl
cl
cl
c
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
cl
el
cl
cl
cl
c
c
c
cl
c
5
5
5
5
5
6
5
5
5
5
5
6
5
5
5
5
5
5
5
5
5
5
6
5
5
5
5
6
5
5
6
5
6
5
5
5
5
5
5
1.012
1.011
1.007
1.016
1.009
1.024
1.022
1.008
1.010
1.007
1.012
1.007
1.017
1.006
1.008
1.017
1.019
1.014
1.012
1.014
1.015
1.010
1.011
1.007
1.027
1.017
1.020
1.026
1.014
1.030
1.014
1.012
1.014
>1,035
1.012
1.007
1.032
1.009
1.011
s
s
s
y
s
py
y
s
s
s
y
s
s
s
s
py
s
y
5
S
S
s
py
s
y
s
s
y
s
y
py
s
s
y
y
s
y
s
s
8.0
6.5
8.0
9.0
8.0
7.0
9.0
9.0
7.5
8.0
8.0
8.0
8.0
8.0
9.0
8.0
6.S
8.0
8.0
7.0
8.0
8.0
8.0,
7.0
9.0
9.0
6.5
7.0
9.0
6.5
6.5
8.0
6.5
9.0
7.0
6.5
6.0
6.5
6.0
tr
tP
tr
1 +
tr
tr
tr
tr
ng
ng
tr
tr
1+
ng
tr
ng
ng
tr
tr
tr
tr
ng
tr
ng
1 +
tr
ng
tr
tr
tr •
tr
1+
tr
1+
tr
tr
tr
tr
ns
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
,ng
ng
ng
ng
ng
ng
ng
tr
na
ng
"9
ng
ng
ng
"3
ng
ng
1+
ng
ng
ng
ng
ng
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
10ery\ul
ng
ng
10ery\ul
ng
ng
ng
ng
10ery\ut
ng
ng
"9
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
D-99
-------
SUBCHRONSC TOX1CITY OF ORTHO-CRESOU IH SPSAGUE DAWLEY RATS
MALE MICROSCOPIC URINALYSIS DATA
[Interim Sacrifice]
ANIMAL NO. RSC/HPF USC/HPF EPI/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
DOSE LEVEL
0 nig/kg/day
50 mg/fcg/day
175 mg/kg/day
600 mi/kg/day
2881
2882
2883
2884
2885
2336
2337
2868
2889
2890
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2947
2948
2949
2950
2951
2952
2951
2954
2955
2956
2980
2981
2982
2983
2985
2986
2987
2988
2989
0
0
0
0
0
0
0
0
0
0
0
0
Q
Q
0
Q
0
0
0
2-3
0
0
Q
0
0
6
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
Q
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
'0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0 '
0
0
0
0
0
0
0
0
0
n
n
n
tp
n
tp
n
n
tp
n
«P
tp
n
n
n
n
n
tp
tp
n
tp
n
tp
n
tp
tp
n
tp
tp
CO
tp
n
tp
tp
n
n
n
n
n
f
f
n
f
n
n
m
f
n
f
f
n
n
n
n
n
n
f
n
f
n
n
m
n
m
f
f
n
n
n
n
n
n
nun
n
f
f
f
n
num
m
f
m
f
num
num
m
f
f
m
f
f
m
m
f
m
m
nurn
mod
num
m
m
f
num
m
m
f
nun
num
m
in
m
nun
f
m
m
m
f
D-1QQ
-------
SUBCHROMIC TOXICITY OF QRTHQ-CRESQL IN SPRAGLIE DAUIEY RATS
HALE URJNAlfSlS DATA
tTerm'inal Sacrifice]
Animal no. App. Vol'. (ml) Sp,-Gr, Color pH Protein Glucose (Cetones Uro. Bili. Slood Hgb,
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2994
2996
2998
2999
3001
3003
3005
3007
cl
hz
c
hz
hz
hz
el
cl
cl
hz
hz
cl
cl
hz
hz
cl
•cl
hz
hz
hz
hz
hz
c
hz
cl
hz
hz
cl
hz
hz
c
cl
hz
c
hz
c
hz
hz
hz
cl
15
14
15
15
7
15
15
15
9
15
15
9
12
15
13
15
15
14
12
15
10
14
15
15
15
15
15
15
8
10
13
15
15
15
15
15
13
15
15
14
1.030
1.027
1.012
1.019
1.025
1.023
1.028
1.026
>1.035
1.013
>1.035
>1.035
1.019
1.018
1.021
1.035
1.012
1.021
1.014
1.033
1.032
1.030
1.022
1.025
1.030
1.016
1.014
1.013
>1.035
>1.035
1.029
1.020
1.019
>1.035
1.032
1.023
>1.035
1.017
1.025
1.030
y
y
s
y
y
y
y
a
y
s
s
y
6
S
y
y
a
y
a
y
y
y
s
y
y
s
s
a
S
a
y
s
s
Y
s
a
y
s
s
y
6.0
7.0
8.0
9.0
6.0
7.0
8.0
7.5
6.0
9.0
7.5
9.0
8.0
9.0
8.0
9.0
7.0
6.5
6.5
7.0
7.0
5.5
7.0
8.0
7.0
9.0
7.5
9.0
6.0
6.0
9,0
9.0
7.5
5.0
6.5
5.0
6.0
7.5
6.5
6.0
1+
2+
* tr
1 +
1+
2+
2+
1+
2+
1+
1+
1+
1 +
ng
tr
2+
1 +
1+
1+
1+
1*
tr
1+
2+
2+
1+
2+
2+
2+
2+
2+
2+
tr
1+
2+
tr
tr
2+
ng
tr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr ,
nr
nr
nr"
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
"9
ng
1+
ng
1 +
ng
1+
ng
ng
ng
ng
ng
ng
1 +
ng
1 +
1+
ng
ng
ng
ng
ng
ng
ng
ng
ns
1 +
ng
ng
ng
ng
1+
1 +
1*
1 +
ng
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ns
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ns
ng ,
ng
ng
ng
ng
ng
ng
ng
- ng
ng
10ery\ul
ng
ng
ng
ng
10ery\ul
ns
ng
ng
ng
ng
1Qery\ul
ng
ng
50ery\'jl
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
D-101
-------
SlJaCHRQNlC TOXICITY OF ORTHO-CRESOL IN SPRAGUi DftUlET RftTS
MALE MICROSCOPIC URINALYS1S DATA
[TERMINAL SACRIFICE]
AMIMAL NO, R3C/HPF USC/HPF EPI/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
DOSE LEVEL~
0 mg/kg/day
50 mg/kg/day
175 mg/ks/day
600 mg/kg/day
2891
Z892
2893
2894
2895
2896
2897
2S9S
2899
2900
2924
2925
2926
2927
2928
2929
2930
2931
2932
2933
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2990
2991
2994
2996
2998
2999
3001
3003
3005
3007
0
0
0
0
0
•2-3
0
0
0
0
0
'0-1
"0-1
0
0
0
0
0
0
•2-3
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
•1-2
0
0
0
0
0
0
•2-3
0
0
0
0
.0
0
0
0
0
0
0
0
•0-1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
' 0
0
0
a
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
a
0
CO
CD
tp
tp
CO
tp
tp
n
CO
tp
n
tp
n
tp
tp
tp
CO
CO
co\tp
co\tp
tp
CO
tp\eo
tp\co
CO
tp
CO
tp
tp
co\tp
tp
tp
CO
CO
CO
co
CO
n
n
CD
f
f
n
n
n
f
n
n
n
f
n
n
n
n
m
m
n
. n
f
f
n
f
n
n
n
f
f
f
n
n
n
n
f
n .
m
1
n
f
n
n
m
m
f
f
m
m
n
m
f
f
f
m
f
m
n
n
n
n
f
n
m
m
n
n
f
f
m
nun
ID
f
f
f
n
f
m
f
f
m
nura
f
D-102
-------
SUSCHRONtC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAWLEY RATS
FEMALE UR1NALYS1S DATA
(Interim Sacrifice]
Animal tio. App. Vol. (ml) Sp. Gr. Color pH Protein Glucose Ketones Uro. Bili. Blood Kgb,
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
3013
3014
3015
3016
, 3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
30B2
3083
3084
3085
3086
3087
3088
3114
3115
3116
3117
3118
3119
3120
cl
cl
hz
cl
cl
c
cl
cl
cl
cl
c
cl
c
cl
cl
cl
cl
cl
el
c
cl
hz
cl
c
cl
cl
cl
cl
cl
cl
cl
c
cl
c
cl
cl
cl
5
5
5
5
5,
5
5
5
5
5
5
5
5
6
5
5
5
5
5'
6
5
5
5
6
5
5
5
5
5
5
5
5
6
5
5
5
5
1.023
1.012
1.006
1.029
1.037
1.027
1.014
1.016
1.015
1.026
1.014
1.018
1.010
1.015
1.014
1,016
1.028
1.009
1.022
1.008
1.012
1.007
1.017
1.009
1.016
1.011
1.016
1.010
1.008
1.011
1.019
1.020
1.019
1.006
1.016
1.014
1.015
py
s
s
y
y
y
s
s
s
py
s
py
s
py
y
py
y
s
y
s
s
s
s
s
s
s
s
s
y
s
y
y
py
s
py
y
py .
8.0
7.0
8.0
9.0
8.0
6.0
7.0
8.0
9.0
9.0
9.0
9.0
6.5
8.0
8.0
9.0
8.0
8.0
9.0
6.5
7.0
8.0
9.0
6.5
7.0
7.0
8.0
6.5
8.0
9.0
8.0
6.0
6.0
8.0
9.0
9.0
6.5
tr
ng
"ng
tr
2+
ng
tr
tr
ng
"3
ng
tr
tr
ng
tr
ng
1+ .
ng
tr
ng
tr
ng
ng
ng
tr
tr
tr
tr
ng
tr
ng
ng
ng
ng
ng
tr
tr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
1+
ng
tr
ng
tr
ng
tr
ng
ng
tr
ng
ng
ng
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
tr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
«9
D-103
-------
SU8CHRONIC TQXICITY OF ORTHO-CRESOL IN SPRAGUE DAHLEY RATS
FEMALE MICROSCOPIC URINALYSIS DATA
[Interim Sacri f ice]
ANIMAL NO. R8C/HPF WBC/HPF EPi/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
175 rng/kg day
600 mg/kg/day
3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3079
3080
3081
3082
3083
3034
3085
3086
3087
3088
3114
3115
3116
3117
3118
3119
3120
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
• 0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
Q
0
0
0
•0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
" 0
0
0
• Q
0
0
Q
0
Q
0
0
0
0
o
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
n
tp
n
tp
tp
n
n
tp
n
tp
tp
n
n
tp
tp
tp
tp
n
tp
n
n
tp
tp
n
«P
n
n
n
tp
tp
n
n
n
n
n
tp
CO
f
n
n
n
f
n
n
f
n
n
n
n
n
f
m
n
m
m
m
n
n
f
n
n
f
n
n
f
n
f
f
f
n
f
n
f
f
n
m
f
m
num
f
m
nun
m
m
f
m
f
m
num
m
n
m
num
f
m
m
f
f
m
m
f
f
m
f
n
f
•f
n
m
f
f
D-104
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
FEMALE URINAIYSIS DATA
[Terminal Sacrifice]
Animal no, App. Vol. (ml) Sp. Gr. Color pH Protein Glucose Ketones Uro. Bill. Blood Hgb.
DOSE LEVEL
0 mg/kg/day
50 fag/kg/day
175 mg/kg/day
600 rag/kg/day
3023
3025
3026
3027
30Z8
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3130
3135
3136
3139
hz
c
hz
hz
c
hz
c
c
c
cl
hz
hz
c
c
hz
c
hz
hz
hz
cl
hz
hz
c
hz
cl
hz
hz
cl
c
e
c
c
hz
12
13
9
13
2
14
4
13
9
6
15
12
15
15
14'
4
13
14
14
11
5
5
10
5
15
15
15
11
13
14
15
10
15
1.021
1.011
1.022
1.028
>1.035
1.025
>1.035
1.026
>1.035
>1.035
>1.035
1.035
1.027
1.009
1.017
1.031
1.015
1.016
1.024
1.013
>1.035
1.032
>1.035
>1.035
1.016
1.014
1.019
1.013
1.018
1.027
1.020
1.019
1.024
y
y
y
y
y
s
y
8
y
y
s
y
y
s
y
y
s
y
y
a
y
Y
y
y
s
s
iy
y
iy
• s
s
y
s
7.0
6.5
5.5
9.0
5.5
9.0
8.0
6.5
6.0
9.0
7.0
9.0
6.5
9.0
9.0
5.6
7.0
7.0
6.5
9.0
5.5
7.5
6.0
6.0
9.0
6.5
6.0
9.0
6.0
6.0
6.0
8,0
5.5
tr
ng
• tr
2+
1+
ng
2+
tr
1 +
2+
tr
2+
tr
ng
1+
tr
lr
tr
ng
1 +
tr
ng
2+
2+
1+
ng
tr
1+
1+
tr
1+
tr
1+
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
1*
ng
1+
ng
1+
ng
"9
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
1 +
1*
1+
ng
ng
ng
ng
ng
1+
1 +
"9
1+
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
nr
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
"9
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
ng
10ery\ul
ng
ng
ng
ng
ng
1Cery\ul
ng
ng
ng
ng
"3
ng
ng
ng
D-105
-------
SUBCHRONIC TCX1CITY QF ORTHO-CRESOL IN SPRAGUE DAUltT RATS
FEMALI MICROSCOPIC UR1NALYSIS DATA
[TERMINAL SACRIFICE]
ANIMAL MO. R3C/HPF HBC/HPF EPJ/HPF CASTS/LPF CRYSTALS YEAST BACTERIA
DOSE LEVEL"
0 mg/kg/day•
50 mg/kg/day
175 mg/kg/day
600 mg/kg/day
3023
, 3025
3026
3027
3028
3029
3030
3031
3032
3056
3057
3058
3059
3060
3061
3062
3063
3064
3065
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3130 '
3135
3136
3139
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
o •
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
• 0-1
0
0
'0-1
'1-2
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CO
CO
CO
tp
CO " '
tp
tp
CO
tp
co\tp
co\tp
' tp
CO
tp
CO
n
co\tp
CO
co\tp
tp
CO
tp
CO
n
CO
n
CO
tp
tp
tp
CO
tp
n
f
f
n
n
n
f
n
f
f
n
n
n
f
n
n
n
n
n
n
n
n
m
n
n
n
f
f
f
f
n
m
m
n
m
m
n
f
f
m
f
f
m
m
f
f
f
f
f
m
f
m
f
n
f
n
f
f
m
m
m
f
m
f
f
f
f
D-106
-------
Study No. 5221.06
APPENDIX E
OHfTH&IMODDGY REPORT
E-l
-------
-------
Study No. 5221.06
SUBCH8DNIC TOXtem OF ORIHO-CHESOL
IN SPRAGUE DAWLEY EATS
ABBREVIATION CODES
Eve Examinations
rtvl = no visible lesions
dead = unscheduled death
A = os (left eye) early retinal degeneration
B = focal retinal degeneration
na = no data available
E-2
-------
-------
EY £ • C L I N 1C
F Q g • A N I M_A_L j
2 4 .1985
Nancy M. Bromberg, V.M.D., M.S.
Qiotomate, American College of Veterinary Ophthalmologists
41(55 Brandywine Street, Northwest
Washington'D.C. 20016
202/383^303
Barry S. Levine
Microbiological Associates Inc.
5221 River Road
esda, BD 20816-
SUBJECT: Study #5221.06
OPHTHALMIC
FINDINGS;
240 Sprague-Dawley rats (120 male, 120
ophthalmoscopically examined Sept. 13,
No Visible Lesions identified
female}
1985 -
E-3
-------
Nancy M. Bromberg, V.M;D., M.S.
Diplomats, American College of Veterinary Ophthalmologists
4105 Brandywine Slreet, Northwest
Washington, D,C. 20C16
202/363-7303
EYE
C
FOR'ANIMAIS
January 2 , 1986
Barry S. Levine, D.Sc., DABT
Microbiological Associates Inc.
5221 River Road
Bethesda, MD 20816
SUBJECT: Oph thalmoscopic Evaluation of Rats.,
Study 5221.06 December 19, 1985
Abnormalities Identified: Rat 2938, male group II - early
generalized retinal degeneration Os
Rat 3058, female group II
focal area of retinal degeneration Os
Due to the infrequent and uni-ocular occurrence of. the
abnormalities, I do not believe them to be compound-related.
All other animals examined had no visible lesions.
A
Naricy ^KT B/*omberg, V.
Dip, , JWC/V.O.
D., M.S.
E-4 .
-------
MEMORANDUM
December 9, 1986
TO : File Study No. 5221.06
FROM : Barry Devine wl^
SUBJECT: Qphttialmoscopic Examination
Terminal ophthalmoscopic examination was on 12/12/85 as reported in
the raw data evaluation form of 12/12/85 signed by Dr. Bromberg.
Her letter of 1/2/86 inadvertently gives the examination date as
12/19/85.
Dr. Bromberg's letter of I/2/B6 also misdesignated animal number
2938, male group II as having early generalized retinal
degeneration, whereas the raw data evaluation form, signed and dated
12/12/85 gives this observation for animal number 2939.
E-4a
-------
-------
SUBCHROMIC TQXICITY QF ORTHQ-CRESQL 1M SPRAGUE DAWLEY RATS
HALE EYE EXAMINATIONS
Animal no. PRETEST-Right Eye PRETEST-left Eye TERMSHAL-Right Eye TERHINAl-Left Eye
OOSE LEVEL
0 mg/kg/day
50 mg/kg/day
2881*
2882
2883
2834
2885
2886
2887
2888
2889
2890
2891
2892
2893
2894
2895
2896
2897
2898
2899
2900
2901 '
2902
2903
2904
2905
2906
2907
2908
2909
2910
2914
2915
2916
2917
2918
2919
2920
2921
2922
2923
2924
2925
2926
2927
2928
2929
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvi
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl •
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
-na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
E-5
-------
SUBCHRQNIC TCXICm OF ORTHO-CRESOL IN SPRAGUE DAULEY RATS
HALE EYE EXAMINATIONS
Animal no. PRETEST-Right Eye PRETEST-Left Eye TERMINAL-Right Eye TESHINAL-Left Eye
DOSE LEVEL
50 mg/kg/day 2930
(continued) 2931
2932
2933
2934
2935
2936
2937
2938
2939
2940
2941
2942
2943
175 mg/kg/day 2947
2948
2949
2950
2951
2952
2953
2954
2955
2956
2957
2958
2959
2960
2961
2962
2963
2964
2965
2966
2967
2968
2969
2970
2971
2972
2973
2974
2975
2976
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl ,
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvi
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl "
nvl
nvt
nvl
nvl
nvl
nvt
nvl
nvt
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvt
nvl
nvl
A
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl .
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
E-6
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESQL IN SPRAGUE DAWLEY RATS
MALE EYE EXAMINATIONS
Animal no. PRETEST-Right Eye PRETEST-left Eye TERMINAL-Right Eye TERHINAL-Left Eye
DOSE LEVEL
600 mg/kg/day
2980
2981
2982
2983
2984
2985
2956
2987
2988
2989
2990
2991
2992
2993
2994
2995
2996
2997
2998
2999
3000
3001
3002
3003
3004
3005
3006
3007
3008
3009
nvl
nvl
nvl
•nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl . -
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
dead
dead
nvl
dead
nvl '
dead
nvl
nvl
dead
nvl
nvl
nvl
dead
RVl
dead
nvl
dead ,
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
dead
dead
nvl
dead
nvl
dead
nvl
nvl
dead
nvl
nvl
nvl
dead
nvl
dead
nvl
dead
nvl
E-7
-------
SUBCHRONIC TOXICITY OF ORTHC-CSESOL IM SPRACUE DAWLEY RATS
FEHALE EYE EXAMINATION
Animal no. PRETEST-Right Eye PRETEST-Left Eye TEftMINAL-Right Eye TERMlNAL-Left Eye
DOSE LEVEL
0 mg/kg/day
50 mg/kg/day
'3013
3014
3015
3016
3017
3018
3019
3020
3021
3022
3023
3024
3025
3026
3027
3028
3029
3030
3031
3032
3033
3034
3035
3036
3037
3038
3039
3040
3041
3042
3046
3047
3048
3049
3050
3051
3052
3053
3054
3055
3056
3057
3058
3059
3060
3061
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
r.vl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
. nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
'na
na
na
na
na
nvl
nvl
8
nvl
nvl
nvl
E-8
-------
SUBCHRONIC TOXICITY OF QRTHG-CRESQl IN SPRAGUE DAULEY RATS
FEHALE EYE EXAMINATION
Animal no. PRETEST-Rigbt Eye PRETEST-Left Eye TERMINAL-Right Eye TERHiNAL-Left Eye
DOSE LEVEL
50 mg/ kg/day 3062
(continued) _*306J
3064
3065
3066
3067
3Q6S
3069
3070
3071
3072
3073
3074
3075
175 mg/kg/day 3079
3080
3081
3082
3083
3084
3085
3086
3087
3088
3089
3090
3091
3092
3093
3094
3095
3096
3097
3098
3099
3100
3101
3102
3103
3104
3105
3106
3107
3108
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
.nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na .
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
E-9
-------
SU8CHRON1C TOXICITY OF ORTHO-CRESOl IN SPRAGUE DAWLEY RATS
FEMALE EYE EXAMINATION
Animal no. PRETEST-Right Eye PRETEST-Left Eye TERMINAL-ftight Eye TERMIHAL-Left Eye
DOSE LEVEL
600 mg/kg/day
3112
-3113
3114
3115
3116
3117
3118
3119
3120
3121
3122
3123
3124
3125
3126
3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl1
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
nvl
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
na
nvl
nvl
nvl
dead
dead
dead
dead
nvl
nvl
dead
dead
nvl
dead
dead
dead
dead
na
na
na
na
na
na
na
dead
dead
dead
dead
dead
dead
dead
nvl
nvl
nvl
dead
dead
dead
dead
nvl
nvt
dead
dead
nvl
dead
dead
£-10
-------
APPENDIX F
PATHOUDGY REPORT
F-;
Study No. 5221.06
-------
-------
TABLE OF CONTENTS
PAGE
I. PATHOLOGY NARRATIVE 1-1
1!. PROJECT SUMMARY TABLE 11-1
ill. TABULATED ANIMAL DATA 111-1
IV. GROSS VS. MICROSCOPIC FINDINGS
Terminal Sacrifice IV-1
Interim Sacrifice IV-48
V, QUALITY ASSURANCE REPORT V-1
APPENDIX 1 REPORTS CODE TABLE
APPENDIX 2 ABBREVIATION LIST
-------
-------
Pathology Associates, Inc.
IjamsviHe, m-.
(301) 663-1644
SUBCHRONIC TOX1CITY OF ORTHQ-CRESOL
IN5PRAGUEDAWLEYRAT5
PREPARED FOR
MICROBIOLOGICAL ASSOCIATES, INC
-------
-------
PATHOLOGY NARRATIVE
-------
-------
SUBCHRONIC TOXICITY OF ORTHO-CRESOL
IN SPRAGUE DAWLEY RATS
Experiment No. 5221.06
PATHOLOGY REPORT
INTRODUCTION AND METHODS
A 13 week gavage study was conducted on Sprague Dawley rats to
determine the toxlcity of o-cresol Male and female rats were divided Into 5
groups at study initiation;
Dose Level Num ber of An i mals
Treatment ( mg/kg/day) Mala _Fero.alB
1 Negative Control Vehicle only 30* 30*
2 o-cresol 50 30* 30*
3 o-cresol 175 30* 30*
4 o-cresol 600 30* 30*
5 Baseline clinical ---- 10** 10**
pathology
* 10 animals sacrificed during test week seven( interim sacrifice); 20 sacrificed at 1 3 weeks
for histopatholog^ with 1 0 having blood collected for clinical patholog^ terminal sacrifice)
**Sacriffced prior tostucfy Initiation
Animals were gavaged daily, 7 days a week, for 13 weeks with 0, 50,
175, or 600 mg/kg of o-cresol in a corn-oil vehicle at 5 ml/kg body weight
At the interim sacrifice, all scheduled rats were killed using carbon dioxide
gas and were necropsled. All required tissues (see below) were fixed In
formalin for possible future evaluation. At the 13 weeks terminal sacrifice,
all surviving rats were killed using carbon dioxide gas and were necropsied,
Body and organ weights (heart, liver, spleen, brain, kidneys [individually],
gonads [individually], adrenals, and thyroids/parathyroids), were recorded for
all rats at terminal sacrifice. AH tissues specified by the protocol were
fixed in 10% neutral buffered formalin: all gross lesions, brain, eyes,
pituitary, salivary glands, heart, thymus, thyroids (with parathyroids), lungs
(with mafnstem bronchi), trachea, esophagus, stomach, small and large
Intestines, adrenals, pancreas, liver, kidneys, urinary bladder, testes,
prostate, ovaries, corpus and cervix uteri, spleen, bone (with marrow),
skeletal muscle, lymph node, spinal cord, mammary gland/skin, aorta, sciatic
nerve.
1-1
-------
Fixed tissues were trimmed, dehydrated, embedded in paraffin,
sectioned at Sum and stained with hematoxyiin and eosin. Representative
sections were examined from all control, mid (175 mg/kg) and high (600
mg/kg) dose rats^of both sexes (due to a high early death rate in 600 mg/kg
dose rats, all mid dose rats'had complete hlstopathologic examinations).
Gross lesions from low dose (50 mg/kg) terminal sacrifice rats and from
Interim sacrifice rats were evaluated and are listed in table form In Section
IV of this report (GROSS VS. MICROSCOPIC FINDINGS). Since complete
histopathologic examinations were required by protocol on all early death
rats and since the terminal sacrifice high dose animals had several early
deaths, one early death high dose male (*2984) and 3 early death high dose
females (*3H2, *3113, *3121) originally scheduled for the 7 week interim
sacrifice were tabulated with the 13 week terminal sacrifice rats,
Additionally, potential target organs (kidney in male and female) were
evaluated for all low dose (50mg/kg) rats,
Results from all complete hlstopathologic examinations as well as all
target organs In low dose terminal sacrifice rats were recorded Into a
computer which required an accounting for every organ listed in the protocol.
The computer generated tables are included In Sections II and ill of this
report (PROJECT SUMMARY TABLE and TABULATED ANIMAL DATA).
RESULTS
Kidney was considered a potential target organ since a slight Increase
In Incidence of minimal renal nephropathy (minimal nephropathy consisted of
2 or more tubules with degeneration/regeneration and interstitial-foci of
chronic Inflammatory cells) was noted in the mid dose rats (15 mid dose
males compared to 10 control males, and 3 mid dose females compared to 5
control female). Findings at all dose levels, however, were not statistically
significant by Fishers Exact Test.
Certain lesions noted in the lung of both control and dosed rats were
suggestive of infection with an adventitious agent These lesions consisted of
perivascular lymphocytlc infiltrate, and scattered foci of Interstitial chronic
inflammation. No specific etlological agent was noted.
Twenty-eight early deaths occurred In high dose rats: 19 high dose
females (3 of these rats were originally scheduled for the interim sacrifice)
1-2
-------
and 9 high dose males (1 of these rats was originally scheduled for the
Interim sacrifice). Pulmonary lesfons noted in these early death animals are
summarized;
Higft dose High dosa
Male . Female
Oildroplets(minimal tomoderate) 8/9 15/19
Congestion (mild to moderate) 8/9 .14/19
. Edema (minimal to severs) 6/9 . 16/19
Hemorrhage (minimal) 2/9* " S/19
* Two additional high dose males surviving to final sacrifice also had minimal to mild
pulmonary hemorrhage (total of 4).
Clinical observation records were reviewed. Death in the majority of
these animals was probably related to lung lesions. These lesions, however,
were considered to be secondary to clinically-noted neurological signs rather
than due to gavage/technician error for the following reasons. There was no
evidence of esophageal or trachea! tears and tracheal inflammation/
hemorrhage was evident only In 1 rat Deaths occurred only in high dose rats.
Clinical observations of tremors, convulsions and comatose condition shortly
after dosing were noted No foreign body pneumonia (frequent consequence of
gavage error) was noted-except in one high dose female rat (*3I35) which
showed typical clinical signs of gavage error (oil around mouth and gasping
after dosing) and in 2 vehicle males (all three of these rats survived to
terminal sacrifice).
A few lesions (increase In mandibular lymph node congestion and
hemorrhage, liver congestion) in these high dose animals wert interpreted as
consequences of spontaneous death. Other lesions (decrease In splenic
hemosiderosis and chronic hepatic inflammation) were related to presence of
mild autolysis or early death in these high dose rats. None of these lesions
was considered significant
Additional lesions were of low incidence and/or equally distributed
between control and dosed animals and were considered incidental lesions
commonly seen in this age and strain of rat
1-3
-------
SUMMARY AND CONCLUSIONS
Sprague Dawley rats of both sexes were gavaged once a day, 7 days a
week for 13 weeks with 0, 50, 175, or 600 mg/kg of o-cresol in a corn-oil
vehicle.
Lesions noted In the lung of both control and dosed rats were
suggestive of infection with an adventitious agent. No specific etiological
agent was noted.
Early deaths occurred in 9 high dose males (1 of these rats was
initially scheduled for interim sacrifice) and 19 high dose females (3 of these
rats were initially scheduled for interim sacrifice). Lung lesions (oil
droplets, congestion, edema) noted in these rats may have been the
consequence of aspiration due to convulsions which occurred after dosing. No
neuropathology was evident for these clinically noted, apparent compound-
and dose-related neurological effects.
In conclusion, no target organ was apparent Early deaths were
associated with clinically observed neurological signs without evidence of
neuropathology.
Diana S. Copeland, D.VJ1
Dlplomate, A.C.V.P.
May 23, 1986
1-4
-------
II. PROJECT SUMMARY TABLE
-------
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESQL
STUDY NO. 5221.04
SPRAGUE-imEY RATS
Pr
SimW: Incidence
PROJECT ID'. NO: OCRESfll
DAYS; ALL
GROUP:
NUMBER OF AN1WAIS:
KWIN
SCIATIC NERME
SPIWL CORO
HUE
BONE WRROU
SAL1WRV ilANQ
LWHflCYTIC INFILTRATE
HflNOIIUWR LWH NODE
CDN5ESTIDN
ITWPHOJO HffERPLASW
Timiys
mORRWSE, ACUTE
n^CREAS
LWPHOCfTIC IHF1L7W7E
HiMOSIOEROSJS
oject Summary Table
a-f NEOPWST3C and MW-NEDPWSTIC
MTES: AH
SEX; MALE
O.OHS/KG 50 HS.KG
20 20
1 1
i Ex 20 8
1 Ex 20 D
1 Ex 20 0
i Ex 2J 0
1 Ex 20 0
I Ex 20 0
0 0
1 Ex 20 0
a o
? 0
1 EJ 20 C
id 0
1 Ex 20 0
0 0
2 0
INFWM^TJOH, CHRDN1C-ACI1VE 1 0
ACIWR ATRDPHf
PITUITARY
CYiT
1 0
1 Ex 20 0
a o
(Sfcport Continued)
II-l
Microscopic
17*BXK6
20
,
20
• 20
20
20
20
20
i
28
0
?
2fl
U
20
1
0
1
I
20
1
Finding!
500MG/KS
21
,
2!
21
21
21
21
20
(1
20
3
9
20
1?
1?
5
i
0
0
21
0
-------
ASSOCIATES
DSTHO-CRESOL
STUDY NO. 5221.06
$?RA6UE-DAUL£Y RATS
INC
Proj e
c t Summar
y
Tabl e
SUHSRY: Incidenc* of HEOPLAST1C and NON-NEOPLASTIC Microscopic
PROJECT ID-: NO: OCRESOL
DAYS: ALL
GROUP;
MJ1BER OF (WIHALS:
THYROID
EPITHELIAL CYST
LWHOCYTIC INFILTRATE
INFWtWriGN, GMNULiMIQUS
PARATHYROID
TRACHEA
LYNPHOCYT1C INFILTRATE
03N6EST1DN
INFLATION, ACUTE
DILATION, GLANDS
ESOPHAGUS
INFLAmVHON, CHRONIC
AOSEWL SLAW
ECTASIA, HEBULW
LLN6
LYNPKOCYTIC ]NF1LTRATE,PERJV
1WW, lOTERfTlTIAL CHRONIC
OIL DROPLETS
CONGESTION
EM»
HEMRRWiGE
OSSEOUS METAPLASIA
MINE1MLJ2ATION, UESSEL
HlSTIOCYTOSiS
PNEIHONIA, FOREIW iflDY
M. HYPERTROPHY, VESSELS
MCTERIA
HMfTT
INFWitMTION. CHRCK1C
FATES: AH
SEX; mil
fl.OMtt/KB SO
2Q
1
i Ex 20 '
10
1
0
1 Ex 1?
1 Ex 20
I
0
0
0
t Ei 20
a
1 Ex 20
4
I Ex 20
13
9
0
0
0
0
0
0
2
2
Q
0
1 Ex 20
10
KG
2(3
i
0
0
fl
a
0
g
0
9
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Q
0
fl
0
•KG I7TO/KQ
20
1
20
11
i
0
20
2tt
1
0
0
I
19
0
20
?
20
i?
11
0
0
0
0
i
2
1
1
0
0
20
12
Findings
430MS/KS
21
I
20
9
2
1 -
20
20
1
1
t
0
21
2
21
3
21
U
7
8
8
t,
4
9
8
5
0
1
1
21
3
II-2
(Rtporl Continued)
-------
r-r-i * ii -^j
Pr
SlftlARY; Incidence
PROJECT 10," NO: OCRESOL
MYS: ALL
GROUP:
NUHEi OF iWNftlSi
AORTA
COLON
DUQDENU1
F8RESWMCH
GLANDULAR STOHflCH
DILATION, SUM)
SKIN
fWfUWf 6Lf«D
SKELETAL MU1CLE
LIMER
INWRCT, WUWTE LOSE
FIBROSIS
CON6ESTION
IHFWtWTlflN, CHRONIC
NECROSIS, CM6ULATWE
LYWHOCTTIC INFILTRATE
SPLEEN
HEMOSIDEROSIS
EMH
CYST
ora-CRisoi
STUDY NO, 5221, Da
SPRAGUE-OrWLEY RATS
oject Summary Tal
of NEOPWST1C ind NCN-WEDPLASTIC
FATES; ALL
SDC; mif
O.OHG/KG 50 HG.KG
20 20
1 i
* Ex 20 0
1 Ei 20 0
1 Ex 20 0
i Ex 20 fl
1 Ex 20 0
I I
1 Ex 20 8
1 Ex U 0
1 Ex 20 0
1 Ex 20 0
o a
i 0
0 0
3 0
i 0
0 . 0
1 Ex 20 0
10 0
a o
i 0
(Report Continutdl
II-3
1 INt*. .
bl e
Microscopic
I73WXG -
20
1
20
29
20
20
20
0
20
H
2D
20
1
0
0
3
fl
1
2D
10
0
0
Findings
dWNB/ra
21
i
21
20
1?
2S
21
2
2S
IS
21
21
i
0
3
i
1
1
2J
8
1
0
-------
PATHULOUY AisSOCl A I tb ,
OKTHO-CRESOL
STUDY NO. 5223 ,U
SPfWGUE-MULEY RATS
Pr o j e
c t Summar
X
Tab! e
SIMttRY; Incidence of NEOPWST1C and NON-NEOPLAST1C Microscopic
PROJECT 10, NO: OCRESOL
DAYS; ALL
GROUP:
NU18ER OF ANIHALS:
KIDNEY
NEPHROPATHY, CHRONIC
INFLATION, ACUTE, PELVIS
LWHQCYT1C INFILTRATE
mmmmmm
URINARY BLADDER
LWHQCYT1C INFILTRATE
CALCULUS
TESIES
ATROPHY, SffllNlFEROUS TUiULE
IffPERPWSift, IKTERSTIT, CELL
PROSTATE
LYHPHOCYTIC INFILTMTi
DUftfff
UTERUS
EYES
CATAIWCT, LENS
RETJfttL ATSOPHY
FATES; All
SEXs MALE
8.0HG/KG 39
20
i
I Ex 20
10
0
2
D
i Ex 20
J
6
f Ex 20
i
0
t Ex 20
11
* Ex -8
1 Es J
* Es 28
8
9
MS.
2D
i
20
9
i
6
i
0
0
0
1
1
i
0
•0
0
(1
0
0
0
KG 17WKS
20
tt
20
15
0
2
0
20
2
3
20
0
ft
20
10
0
9
20
0
i
Findings
iflBMG/KG
21
1
21
i
0
0-
0
21
1
3
21
1
0
21
4
1
5
21
1
9
CERVIX
(Report Continued)
'II-4
-------
PATHOLOGY _ASbOClm"r tS ,
CCTHO-CRESQL
STUDY NO, 5221.04
SPRAGUE-OflULEY IWTS
Project Summary Table
: Incidence si NEOPWSTiC jnd NON-tiEQPLASTlC Microscopic Findings
PROJECT ID, NO: OCRESOL FATESr AIL
MS: ALL SEX: HALE
6MHIPI O.OM5/K8 50 HE.Kfi I75HG/K6
NUMBER OF (SNIWLS; 20 20 20 21
OTHER TISSUES WO LESIONS;
HESENIER1C LN-HEMORRHASE 1 J 0
JN6. LN-LWHOID HYPERPWSIA 1 I 0
r NEO!OS1S I D 1
II-5
-------
IMC
ORTHO-CRESOL
STUDY NO, 5221, U
SPM6UE-MULEY RATS
Project Summary Table
SUftWlY: Incidence of NEflPLASTIC and NCN-NEOPWSTIC Microscopic Findings
PROJECT ID-i NO: OCRESOL
DAYS! ALL
GROUP:
NUMBER OF ANIMALS:
ifWIN
SCIATIC NERVE
SPIfML CQRO
SINE
i!NE mfiROU
SALIWRY GUWCI
NWQIiULAR LWPH NODE
ffiMORIWIBE, «UTE
CONGESTION
IWPH010 HffERPLASM
THWUS
ifHORSHABE, ACUTE
CYST
WNWWS
LWPHOCYT1C INF1LTMTE
fCimt ATROPHY
PITUlTflRY
RST
FATES: fill
SEX; FEWLE
0,flMG/KB 50
20
i
1 Ex 20
1 Ex 20
II Ex 20
1 Ei 20
1 E> 20
I Ex 20
1 Ex 29
3
0
12
lEx 20
13
0
1 Ex 20
3
1
1 Ex 20
0
HG/KO,,
20
H
0
0
0
D
0
0
0
0
0
0
0 •
0
(i
0
0
0
0
0
1731G/KG
20
It
20
20
20
21
20
. 20
2J
0
9
J5
n
16
1
20
2
2
*2fl
1
6DHM5/KB
23
1
22
23
22
23 .
a
23
22
i
7
13
21
14
, 1
21
i
J
22
0
(Report Continued)
II -6
-------
PAl"rlUL.Uu*f
i t is
OTHMRESOL
STUDY NO. 3221. Oi
SPRAGUMJAULR RATS
Pr o j e
c t Summar
y Tab! e
SUTOMYi Incidence oi NEOPLASTY and NQN-NEOPLASTIC
PSOJECT ID" NO: OCRESOL
DAYS: ALL
GROyP:
NIW8ER DFOTWLSs
TKYRQID
EPITHELIAL CYST
LYHPHQCY11C INFILTRATE
MRATHYRDID
TOCHEA
LYMPHOCYTE INFILTRATE
(€HflRRW6i, ACUTE
INFLATION, ACUTE
ESQPWiUS
IWUWffHH, CHHON1C
«RE*L SUttC
ECTASW, MEDULLA
LUNS
LWPHOCYTIC IhFILTTWT£,PE8W
1NF1A1, IHTERSTHML CHRWIC
OIL DIOPLETS
CON6ESI10N
EDEMA
HEMORiJWBE
HI5TIOCYTOSIS
PNEDMIWIA, FORIION BODY
PNEUMONW, CHRONIC-ACTWE
WCTE8W
mm
IHFWtttTlON. CHRONIC
Microscopic
Findings
WES: ALL
SEX: FHW.E
O.QHG/KB 50
20
„
it EX n
13
0
1 Ex IS
1 Ex 21
5
0
0
1 E* 18
0
1 Ex 21!
3
i Ex 2C
I?
8
1
0
0
0
9
0
9
0
II Ex 20
2
HG/KG
20
8
0
I
9
0
0
0
0
0
0
0
g
0
0
0
0
0
1]
0
9
a
0
0
a
0
0
17WK5
20
i
2J
ti
i
U
28
2
8
D
20
fl
20
i
20
20
(,
e
0
a
D
3
0
0
0
20
3
mwm
23
1
22
11
2
18
21
t
S
i
23
i
22
2
23
14
7
15
14
H
5
2
1
2
1
23
I
flflRTA
1 El 20
20
23
II-7
(Report Continued)
-------
WTHO-CRESOL
STUDY NO. 5221.OS
SPRAGUE-MULEY RflTS
Proj
e c t Sumrnar
y Tabl e
SlttWIN: tncidsnci a* NEOPLMTIC and NQN-NE0PLASTIC
PSDJEET IttC NO; flCRESOL
MYS; ALL
GROUP;
WH3ER OF (WmiS:
COLON
KIODENUK
FOiESTQfttCH
CONSKT10N
GWNOUWR STUWCH
SK1H
fWtWfiTf GUWD
SCELETAL MUSCLE
LIVER
C8N6ESTICN
lNFUWWn», CHRONIC
LWHWrniC INFILTRATE
L1PIDOSIS
SPLEEN
H81QSIDEROSIS
FftTES: fill
SEX: FEhWLE
O.CMG/KG 50
20
,
1 Ex 20
I Ex 20
1 Ex 20
2
1 Ex 20
1 Ex 20
1 Ex 28
i Ex 20
t Ex 20
0
7
9
1
4 Ex 20
lo
HE/KG
20
i
0
0
1)
0
a
0
3
D
0
0
0
0
i
0
0
Microscopic
17WKG
20
I
20
20
2fl
1
20
2D
20
20
20
g
2
I
9
20
15
Findings
MOMS/KS
23
,
21
1?
23
a
23
23
23
23
23
3
t
1
1!
21
7
(Report Continued)
11-8
-------
KTHO-CRESQL
STUDY NO, 5221.06
SPWGUE-MULEY SATS
Pr oj e
c t Summar
y Tabl e .
SUttttRY: Incidence e* NEQPUSTIC and NON-NEOFLAST1C
PROJECT IfrfNO: QCRESOl
MYS; flLL
GROUP;
NUMBER OF fWmiSi
KIDNEY
fiPHROPATtff, CHRONIC
1NFWH, CHRONIC-ACTIVE, PELVIS
INFUWfflCN, AOTE, PELVIS
MINERALIZAT1CN
IYMPHOCYT1C INF11TWTE
HYORONEPHROSJS
EP1TK, HfPERPLASIA, PELVIS
CYST
IWNftRY BLADDER
LWHOCYTIC INFIITIMTE
SOWKWS METAPWSIft
INFUW, CHRUUC-flCTIYE
EPHHaiAL HYPERPWS3A
INFLfltWTIlK, ACUTE
TESTES
PROSTATE
(WARY
UTESUS
EYES
WTAfWCT, LWi
IYMPHOCT. INFlLT^TE.mRD.GL
RETIWL ATROPHY
Rrrm SEGENE(WTIIIN
MTEB: ALL
SEX: FTOLE
9.WG/KG 50
20
,
It Ex 20
J
2
3
2
2
I
1
0
1 Ex 20
3
I
1
1
0
f E< 0
1 Ex «
i Ex 28
1 Ex 20
1 Ex 23
3
2 -
D
i
H6/KC
20
i
20
1
0
0
7
5
3
1
S
D
D
3
0
D
0
D
D
D
D
0
0
0
d
0
Microscopic
175HB/KS
20
i
20
3
0
D
2
4
J
0
0
23
o -
fl
0
0
1
8
a
20
20
2B
0
a
3
0
Findings
4GOH6/K6
23
„
2!
4
I
S
1
D
3
3
1
20
0
0
3
0
5
0
t
22
23
23
1
0
1)
a
CERVIX
20
23
(Report Continued)
II-9
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO, 5221.04
RATS
Project Summarx Table
SUtWKY: Incidenct a* NEOPWST1C and NON-NEBPLASTIC Microscopic Findings
PROJECT ID. NO: OCSESOL FATES: ALL
DAYS: ALL SEX; FEM.E
GROUP: fl.OHQ/KO 50 KG/KG !75ha/KS dOOHfi/KS
NUMBER OF (WIHftLS: 20 2D 20 23
OTHER TISSUES «D LESIONS:
(fSEMTERY-FAT NECROSIS 0 0 0
WiWft-HEHDRIWlGE, ACi/TE 0 0 B
«AG1NHNFUW»TIDN, flWTE J U 0
180
008
11-10
-------
III. TABULATED ANIMAL DATA
-------
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOl
STUDY NO, 5221.06
SPRA6UE-W4EY RATS
Tabulated Animal Data
PROJECT 10; OCRESOL GROUP; J.OMG/KS SEX; MALE MYSi ALL
PAGE i MTES; fill
ANIMAL ID, NO: 2891 2892 2893 2B94 2895 Zm 2897 2198 28?? 290J
BRAIN NNNNNNNNNN
SCIATIC mm N NN N N N N N.H N
SPIWtf. CCRO NNNNNNNNNN
IONE NNNNNNNNNN
mi HARIOU NNNNNNNNNK
SALIWRt GLPWO NNNNNNNNNN
IWDIiUWR LWH NODE N N N N N N
LWHOID HYPERPWSIA - - 1 - 1 ' - - - 1 2
THWUS N
HEWORRWGE, flCUTE (i) W <1) <1) <1> CD - <1> <2>
PftNCfiWS NNNNNN NNN
HfflOSIDEROSIS <2> - - -
PITUJTAiW NNNNNHNNNN
(Report Continued)
III-l
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CREBOL
STUDY NO, 5221,06
SPRAGUE-DAULEY W73
O
Tabulated Animal Data
PROJECT ID: GCRESDl GROUP: O.OMG/KG SEX; MALE DAYS: ALL
WSE 2 FATES: ALL
ID. NO; . 2891 28?2 28?3 2B?4 2895 2m 28?7 2898 28?? 2?00
THYIOIO N N N N N
EPITHELIAL CYST (35 (3) (1) (1) - - U?
PARATHYROID • NNNNNNNNNN
TRACHEA NHHNNNNNNK
ESDPWQUS NNNHHNNNNH
NKNNHNNNUN
um
LYHPHDCYTIC INFILTIMTE.PEilV <2> <1> <25 <3> <2>
1NFW1, 1NTESST1TWL CHRONIC - - - (1) <2> (15
HEART N N N N N
INFLATION, CHMN1C <]) <1) <2)
-------
PATHOLOGY ASSOCIATES, INC.
QRTKO-CMSQl
• STUDY'NO, 5221.04
SPRA6UE-OAULEY RATS
Tabulated Animal Data
PROJECT 10: OCfitSOL GROUP; O.OMG/KG - SEX; WLE DfiYS: ALL
PAGE'3 FATES: All
AN1KAL ID, HO: 2891 28?2 2B?3 2B?4 26?S 2B9i 2BJ7 2898 2B99 2?00
FORISIOWCH NNNHNNNNNN
GLWOUWR STWCH H N N «' N ' N N N N
DIWT1CN, GUWD 2
SKIN . HNNNNNNNNN
fWWRY 6UWD NUNNNHUUNN
SKELETAL MUSCLE NNNNNNNKNN
LIVER NNNNNNN N
F1IROS1S ....._. (2)
S, CWBULAT1VE <3)
N N N N N N H
HEMBS1DE80SIS 11
CYST - - - <2> .----•--
KJWEY N N N
NEPHROPATHY, CHSflNIC 1 1 I - I - i - - 2
LYMPHOCrriC MfflLTRATE ---
-------
PATHOLOGY ASSOCIATES, INC.
CRTHO-CRESOl
STUDY NO. 5221,0$
SPRAGUE-WM.EY MTS
Tabu! ated An imal . Data
PROJECT ID; OCRESOL mm?: 8.0KG/KG SBC: HALE DAYS: ALL
PAGE 4 FffTESi ALL
ID, NO; 2891 2892 2853 2S94 29?5 Wi 2897 2890 2199 2900
TESTES NNNNNNNNNN
PROOTTE M N N
IWHQCYTIC INFllTRftTE - - <2) (I) <2) (1) <2) -
EYES HNNNNNNNNH
1II-4
-------
•PATHOLOGY ASSOCIATES, INC.
ORTKQ-CRESOL
STUDY NO, 5221.04
MTS
Tabulated Animal Data
PftOJEiH 10: OCRESOL GROUP; O.OH6/K6 SEX; HALE MYSi ftLl
PASE 5 FfflTS; ALL
ID. NO; 2891 2892 23?3 2S94 23J5 28?5 2897 2898 1899 2900
OTHER TISSUES (5ND LESIWS;
MESENTER1C LN-HEMOfiR»GE 2 -
ING. LH-LWHOID HtPERPWSW 2
(Report Continued)
III-5
-------
PATHOLOGY ASSOCIATES, INC
ORTHSHRESOL
STUDY NO, 5221.Hi
SPRAGUE-EtfULF? RATS
Tabulated Animal Data
PROJECT ]D: CCRESDL GROUP: Q.OHG/KS SEX: Wit DAYS! ALL
PflGE 6 FATES: All
(MWd ID, NO; 2901 2902 2903 29fl4 2905 2901 29(17 2?J8 2909 29!9
NNNNNNNN'NN
SCIATIC NHNE NNNNNNNNNH
CORD NNNNNNNNNN
8DNE NNNNNNNNNH
o
mi mm NNNNNNNN.NN
SALIW1Y 6UWD • NNNNNNNNN'"N
HOT! KJLAR LYMPH NODE N N H N H
LWHOID HYPERPLASW 22-2-22---
WfflUS N N N
HEMflRRWOE, ACUTE <2> <2) (1) (» - - <1> U3 - (1)
WWCREAS N N N N N N N
H9WSIDEROSIS <1)
INFUWttTlffl, CHROKIC-^aWE ,-._.. (2)
AC3NAR ATROPHY <1) -.,-.-
PITUITARY N N UN N N N N~N H
(Rspari Continued)
111-6
-------
PATHOLOGY ASSOCIATES, INC.
OffTHfl-CRESQL
STUDY NO, 5221.U
SPRAGUE-DAULEY MS
Tabulated Animal Data
PROJECT Id OCRESQL GROUP: Q.OKG/KG SEX: Mil DAYS; ALL
PAGE ? FATESi ALL
i ID, NO: 2901 2902 2903 2904 2J05 2904 2907 2M8 2909 2910
THYROID N N N N N
EPITHELIAL CYST - <1) - (1) - <2> <2> - - <2>
LYMPHOCYTE INFILTRATE ... ^ ......
PARATHYROID UNKNNNHNMH
NNNNN NN'NN
LYltfHOCYTIC INFILTMTE <2>
ESOPmGUS NNNNNNNNNN
6LAND N N N N N N
ECTASW, MEDULLA 1 - - i - - 2 - - 1
LUNS N
LYHPKOCYT1C INFILTRATE,PERiy <2> <3) (2) <2) <2) - -
1NFLAH, INTERSTITIAL CHRCNIC (1) (25 - - <2) (1)
HISTICCYTOS5S - - (1> - - <1) - - -
PNEU1CNIA, FORllffl BODY (2)
HEART N N N N N
INFLATION, CHRONIC (!) <1) (2> - - - - <2) - <1)
AORTA NNHNNHNNNN
COLON NNNNNNNNNN
(Report Continuidl
III-7
-------
PATHOLOGY ASSOCIATES, INC.
QRTHO-CRESOL
STUDY NO. 5221.04
RATS
Tabulated Animal Data
PROJECT ID; OCRESOL GROUP; O.OH5/K6 SEX: WLE DAYS; ALL
PAGE 8 FATES: All
DUflDENIH
ID, NO:
2901 29D2 2903 2904 2905 2?U 2m 2908 290f 2915
NNNNNNNNNN
FORESTOWCH
NNNNNNNNNN
GUNDUWI STOMACH
NNNNNNNNNN
SKIN
NNNNNNNNNN
NNNUNNNNNN
SKELETAL MUSCLE
NNNNNKNNNN
LIVER
INFWMftTIDN, CHRONIC
N N N N N
N N
SPLE0<
HEMOS1DEROSJS
N N
1 2 1 1 2 1 2 - - 1
KIDNEY
NEPHROPffTW, CHRONIC
LYUPHflCYTIC INFILTRATE
N N N N
1 - - - - 1 2 1
<1>
URINARY BLADDER
CALCULUS
N N N N - N N
I - 2 2 - - 2
(Report Continued)
II1-8
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO, 5221,04
SPRAGUE-MULFY RATS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP; O.OMS/K3 SH; MALE MYS:
PAGE ? FATES: ALL
ID, NO; ini 2902 2?03 2?04 2905 29U 2907 2?08 2?09 2918
TISIES ' NNNNN MHHH
ATROPKf, SEMINIFEROUS TUBULE <1>
PROSTATE N H N H N N
LYWPHOCYTIC INFILTMTE <2) <1> - - <2>
EYES NNHNNNNHNH
-------
PATHOLOGY ASSOCIATES, INC.
QRTHQ-CRESQL "
STUOY NO, 5221,06
SPRAGUE-MULEY WTS
Tabulated Animal Data
PROJECT ID: OCRESDL GROUP; fl.DHG/KG SEX: HALE MYSr ALL
PAGE 10 FATES: ALL
10, NO: 2901 2W 2?03 2?D4 2f05 21U 2W l?m 2?0? 2910
OTHER TISSUES m LESIONS!
(End
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO. 5221. Oi
SPiWSUE-MWLET RATS
Tabulated Animal Data
PROJECT 10; OCRESCL GROUP: fl.OMS/KC SEX: FEWLE DAYS: ALL
PAGE 1 FATES: ALL
ANIfttL ID. NO; 3023 3U24 3025 302S 3827 3J28 302? 3033 303! 3032
8M1N NNNNNNNNNN
SCIATIC NERUE NNNNNNHNNN
&1WL CORD • NNNNNNNNNN
BONE NNNNNNNNNN
SON! mm NNNNNNNNNN
SAL1MAKY GLAND NNNNNNNNNN
KWBIJLAR LWH NODE N N
LWPHUID HYPERPLASIA 1311-13-22
THYMUS , N N N N
HMRRWSE, ACUTE -
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221.U
SPRftSUE-WLET WTS
Tabulated Animal Data
ADJECT ID: CCRESOL GROUP: O.WG/KG SEXi FEWIE ' DAYS: ALL
PAGE 2 FATEi: ALL
ANIHAL ID. NO: 3023 3(124 3025 3026 3327 3028 3029 3Q35 303! 3032
&
THYROID N N N
EPITHELIAL CYST (2) (1) (1) - - <2> <2) (J) <2>
WRATKYROID NNNUIJHUHNN
TfWCHEA N NNNNNNN
LYMPHOCYTIC INF1LTEATE <1) • (1)
ESOPHAGUS NNNUNNNNNN
NNNNNNNN N
ECTASW, HEDULLA
IONS
LYMPHQCYT1C !NF!LTt»TE,PERiy (1) «> <1) <2> <2)
INFLrtl, INTERSTITM CHRONIC - - <1>
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
• STUDY NO. 5221,06
SPWGUE-MULEY MTS
Tabulated Animal Data,
PROJECT ID: OCRESOL GROUP; O.DHG/KS SEX: FEMALE DAYS; ALL
PACE 3 , FATES; ALL
ANIMAL 10, NO:
DUODENUM
3023 3024 3025 302i '3C27 302S 3029 3030 3031 3032
NNNNNNNNNN
F08ESTONACH '
CDNBEST10N
N.NNNNNNN H
........ 2 -
6WWDUWR STffttCH
NNNNNNNNNN
SKIN
NNNNNH. NNNN
GUftD
NNNNNNNNNN
SKO.E1AL H'JSCLE
NNNNHH-HNNH
LIVER
INFWtWTICN, CHRONIC
NNNH.NNN N
....... <1> - W
SPLEEN
HEHDS3DEROSIS
NNNN
2 ' 2 2 2 2
KJWEY
INFIAK.CHRDNIC-ACTWS.PEWIS
MINERALIZATICN
LYHPHOOTIC JNFILTIWT!
N N N N N
(2) - -
<2> - -
U)
< Report Con tinned)
111-13
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRISOL
STUDY NO, 5221,06
SPRAGUE-DAULEY RATS
Tabulated Animal Data
PROJECT IE): OCSESOL SROyP; fl.OHS/KO SEX: FEmiE DftYS: ALL
PftGE 4 FATES; AIL
ID, NO: 3023 3024 3025 3024 3827 3028 3029 3030 3Q31 3032
8LADOER NNNNNNNN
LYHPHDCYT1C INFILTRATE <1> - - (1)
(WRY NNNNNNNNNN
IfTilUS NNNNNNNNNN
RES NNNNNNNHN
LWHOCY. 1NF1LTMT£,»RD,GL (2)
CERVIX NNNNNNHNNN
(Report Coatinutd)
111-14
-------
PATHOLOGY ASSOCIATES, INC
OmiQ-CRESQL
STUDY NO. 5221,W
SPRAGUE-WW.EY RATS
Tabulated Animal Data
PROJECT ID; DCRESOL SRQUP: 0,TO/KG SEX; FEmiE MYSi ALL
PAGE 5 FATES; ALL
JO. NO; 3D23 3024 3025 3024 3027 3028 3fl2? 3030 303! 3i32
ffTHER TISSUES AND LESHNSs
-------
PATHOLOOY ASSOCIATES, INC.
ORTHQ-CRESOl
STUDY NO, 5221.04
RATS
Tabulated Animal Data
PROJECT ID; OCRESOL SROUPs O.OHG/KS SEX; FEWLE MYS; ALL
PAGE 4 FATES; AU.
10. NO: 3(133 3034 3035 1036 3D37 3038 3039 3040 3041 3042
BRAIN NNNNNNNNNN
SCIATIC NERVE NNNNNHNNNN
CORD NNNNNHNHHN
BONE N'NNNNNNNNN
KM mmw NNNNNNNNNN
SAL2MARY flWD HNNNNNNNNN
LWPH NODE N N N N N N
LYUPHDltt HYPgRPWSlft 3 - - 1 I - ~ • i
"WfflUS N N N
HBWRRHA6E, ACUTE <2> (1) (2> «> (1)
mmm • NNN NHNNNN
IYWHCCYT3C INFILTRATE <»
PITUITARY NNNHNNNNNN
(Report Continued)
111-16
-------
PATHOLOGY ASSOCIATES, INC
OTM-CRESOL
STUDY NO. 5221,06
SPMGUE-MUIEY RATS
Tabulated Animal Data
PROJECT ID; QCSESOL GROUP: O.OHG/KG SEX; FBtfLE DAYS: ALL
WGE ? FATES; ALL
i ID. NO:
TlffSJIO
EPITHELIAL C7ST
3(133 3034 3D35 3034 303? 3038 303? 3040 30« 3fl«
N N N N
(1) 1 <2> <2)
(1!
PARATHYROID
IINNNN
NNNN
TRACHEA
LYHPHOCYTIC 1NFILTMTE
N N N
N N N N
NUNNNNNNNN
(WML 6UWD
ECTASW, MEDULLA
NN^NH NN NK
1 - - 1
LlTiG
LWHOCYTIC
IMFW1, INTERSTITIAL CHRtNIC
HJSTiOCYTOSIS
(2)
<2>
U> <»
(1)
<2>
«»RT
, CHRONIC
NNN NNNNNN
--- .....
AORTA
NNNNNNNNNN
COLON
N N N N N N N N.N N
(Report Cantinusd)
111-17
-------
PATHOLOGY ASSOCIATES, INC.
OSTHO-CRESOL
STUDY NO. 5221, U
SPRAGUE-MULEY »TS
Tabulated Animal Data
PROJECT 10: OCREBCL GROUP: 0.OHO/KG BEX: FB4H.E DAYS: ALL
PftGI 8 FATES; AIL
OUODWUN
10. NO:
3033 3034 3035 3031 3837 3038 3039 3040 3041 3042
NNNNNNNNNN
CONGESTION
NN'NNNNN NN
....... t . .
STQtttCH
NNNNNNNNNN
SKIN
NNNNNHNNNN
HWIWRf SL««
NNNNNNNNNN
SKELETflL MUSCLE
NNNNNNNNNN
IMR
INFLrttttTIDN, CHRONIC
UP1DOSIS
N N
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO, 522144
SPRA6UE-DAULEY RATS
Tabulated Animal Data
PROJECT ID; OCRESOL flRQUP; 0.0H6/KG SEX: FEMALE MYSi ALL
PAGE 9 MTES: ALL
ID, MO: 3033 3034 3035 3034 3037 3038 3039 3040 30-11 3042
KIDNEY •- H N N N N N N
NEPHRWWHY, CHRONIC ...... | ...
N1NEWLIZATIOH -------
saumous METAPLASJA cz) - - -
1NFLAM, CHRCNIC-ACTIVE 2 - - -
EPITHELIAL HYPERPWSJA W
WRY NNHNNNNNNN
UTERUS NN-NNNNNNNN
EYES NHNNNNN N
LYHWOCY. INFILTMTi,HARD,6L CD -
DESENERATIDN 2 - -
NNNNNNNNHN
(Report Continud)
111-19
-------
PATHOLOGY ASSOCIATES, INC.
ORTHQ-CRESOL
STUDY NO, 5221.0(5
Tabulated Animal Data
PROJECT IDs QCRESOL GROUP: fl.OHG/KS SEX: FEMALE WYSs All
PftGE 10 WTESi ALL
ID. NO; 3033 3034 3835 3034 JI37 3038 303? 3040 3041 3042
mm TISSUES
-------
PATHOLOGY ASSOCIATES, INC.
DRTKO-CRESOL
STUDY NO, 5221.J4
SPW6UE-W4EY WTS
Tabulated Animal Data
PROJECT ID; OCRESOL GROUP: 50 H5.K5 SEX: WLE DAYS: AU.
WBE i FATES; ALL
ID. NO: 2924 2925 2m 2927 2928 2929 2930 2931 2932 2933
BRAIN * * * * » » * * * »
SCIATIC NERVE i « » « * * * f § i
SPJWL CORD * « * * * f.» i i I
80NEWRRBU . i i » « « i » » i i
SkLJWRY GU«0 i i f i * i i I « «
NWDJBULAR LYMPH NODE . * * * f * * * * » »
THWUS « * * * • * « * * «
fWCRWS « ' * * * f'» • * i i
PITUITARY • i i f » i * i § i «
THYROID **»iiiiJ*.i
WRATHYROID * * • * * * * * * *
-------
PATHOLOGY ASSOCIATES, INC.
OffTHQ-CRESOl
STUDY NO, 5221,0<
SPMGUE-WJtiY RATS
Tabulated Animal Data
PROJECT ID; (JCRESOL GROUP! 50 HE,KG SEX; fttlE WYS: ALL
PASS 2 FATES; All
ID. NO;
2?25 2?24
* * *
2?28 2?2? 2?30 2?3J 2932 2?33
* » * * ' * i
ISOPWfiUS
ttttittttt
mmi
* » * * * » * * » «
LUNG
HEART
AORTA
» »
» i
* * *
* *
i • i » i ' i i
COLON
9UODENU1
FDRESTOWCH
SWHOULAR STOMACH
SKIN
6WNO
iii»*i*i*'t
* * * * » »*
ttttttiit*
* i
i i
» i
Itilililt*
* » •
i » *
(Report Continued)
111-22
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOl
STUDY NO, 522! ,0d
SP!WGUt-!MLEY SATS
Tabulated Animal Data
PROJECT ID; OCRESUL GROUP: SO HG.KG SEX; WLE »YS; ALL
WGI 3 FATES: ALL
ID. KOi 2924 2925 2m 2927 2928 292? 2?30 2931 2?32 2933
SKELCTflL MUSCLE *»*ii*i*ii
IMR i*iiii»iii
KiCNEY N N
NEPHROMTHY, CHRONIC 1 i - i 1
LYMPHOCYTE 1NFILTWTE - - (I) CD
HYORCNEPHROSIS (2)
UR1WRY ILflOOER
TISTE3 * * * » * * *t*
ATROPHY, SEMINIFEROUS TUBULE 131
HYPEWWSJA, MERSTIT, CRL <2) - - -
PROSTATE * * « » * <* *
EYES . i i * i » i »
(Report Contisuid}
111-23
-------
PATHOLOGY ASSOCIATES, INC
ORTBO-CRESOL
STUDY NO. 5221,01
SPftGUE-MULSY RATS
Tabulated Animal Data
PSOJECT ID: QCRESQL GROUP: 50 HG.K6 SEX; fWLE MYS;
PAGE 4 FATES: AIL
ID. NO! 2924 2925 2?24 2?27 2921 2929 293Q 2931 2932 2933
OTHER TISSUES (W LES1INS;
(Report Continued)
111-24
-------
PATHOLOGY ASSOCIATES, INC,
ORTKC-CRESOL
STUDY NO. 5221,OJ
SPMGUE-WULEY RATS
Tabulated Animal Data
PROJECT ID; OCRESOL SROUPi 50 HB.KS SEX: WL£ WYSi ALL
PAGE 5 FATES; ftll
ANNWL ID. NQ; 2534 2935 293i 2937 2933 273? 2940 2941 2?42
i « i » i i i * i i
SCIATIC NERUE » I • * » 1 * * » *
CORD tiittitttt
* i i t i * i * » i
SINE IWJROU ii**«*-tiji
S5LIWRY 5UWD fiiit*t'i*i
(WDI8UWR LYMPH NODE i * * * * * * « » «
THTMUS » * * » * * * ' * *
WWCRIAS i » t f * i * i J »
PITUITARY * * * » * * * « * »
THYROID » » » * » « » » * *
MftttHYROIQ » » i » * * * * * *
(Report Continued)
111-25
-------
PATHOLOGY ASSOCIATES, .INC
ORTHQ-CRESOL
STUDY NO, 5221.04
SPMGUE-MULEY fWTS
Tabulated Animal Data
PROJECT ID; OCRESOL SROUP: SO HB.K6 SEX: MALE WYS: ALL
PAGE & FffTES: AH
ID. NO; 2934 2935 2934 2937 2938 293? 2940 2941 2942 2943
TRACHW ii»j»»i*ii
ESOPWGUS » * i t * i i i * t
ADRENAL 6LWD » * * * * * * * « *
LING 1 t i * *'i I I i *
HEART titttttttt
DUODENUM ii«*i*tfi*
FQRESTfftfCH
SUWOUWR STH«C« i * » * * i » » * *
SKIN ltiifi*»ii
SUW i i i * * I i i t *
(Report Continued)
111-26
-------
PATHOLOGY ASSOCIATES, INC,
ORTMKRESQl
STUDY NO. 5221,04
SPRACUE-OAULEY RATS
Tabulated Animal Data
PRWECT ID; QCRESOL 6RCUP; 50 MS.K8 SEX: mil MYS; ALL
PAGE ? ' FATES: All
ANIMAL 10. NO: 2934 2?35 2?3i 2937 2?38 2939 im 2941 2?42 2543
SKELETAL MUSCLE » » * » * » » « I «
LIVER iiifii*»*i
SPLEEN Jiiitiifii
KIDNEY
NEPHRQMTHY, CHSflNIC 1 1 I
, ACUTE, PELVIS <1)
URIWRY 8WDOER i*ifiii*i»
TESTES
PROSTATE • i**i*itti*
* » * , * * « » * * *
UliRUS * * * * * • * * t i *
EYES liiiiii**»
CERVIX l * » * * * * t » *
(Report Continued)
111-27
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO, 5221.04
SPRAGUE-M4EY MIS
Tabulated Animal Data
PROJECT ID; QCRESOl GROUP; 50 KG,KG SEXs fttlE MYS; ftll
FACE 8 FATES: All
ID. NO: 2934 2935 2?36 2?3? 2938 293? 2930 29« ZJ« 2J43
OTHER TISSUES AND LESICNSs
(End »f Report)
111-28
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CHBOi
STUDY NO, 5221.06
S?RAGyE-MULEY RATS
Tabulated Animal Data
PROJECT ID; OCRESOL 6RQUP; 50 MS/KS SEX: FEfttLE DAYS; ALL
MGE i FATES: All
ID, NO: 305(5 3857 3058 3059 3040 mi 3042 3043 30*4 3045
SCJflTIC NERVE i * • * * i i i » i
SPimL CORD i i i i i i i i « I
BONE iii»«if!'»i
BONE IViRRDU ^ ii^intiiiit
5ALIWRY SlJiNO » « » * i » t f i i
MW01BULAR LYMPH NODE I i • i i i i i i i i
THYMUS i i * • t * * » * *
fWCREAS i i t i i i 4 E i i
TKYROJD II i 1 i i i i i i
PARATWR010 * » * t * » i * * *
CReport Continyid)
111-29
-------
PATHOLOGY ASSOCIATES, INC.
QRTHO-CREStt
STUDY NO, 3221.06
SPRdBOE-MULEY RATS
Tabulated Animal Data
PROJECT IB: BCRESOl 8ROUP: 50 HG/K6 SEX: FEfttLE DAYS; ALL
PAGE 2 FflTES: All
TRACHEA
ESCPWGUS
ID. HO:
LJNG
HEART
AORTA
COLON
OUODENUH
FORESTttfcCH
BWNOULAR STOMACH
SKIN
GLAND
3056 3057 3(158 3059 3J3iO 3041 3042 3043 30« 304S
I i * j * t » i i i
*i«i«iii*i
» » « * * * i i i i
* * * > * * i,i i *
i t i « « i' i i « i
fi***t*t»*
liitiitlii
ii»>iiti»<
itiiitttii
I • * * » t « t * *
i » i i i
» i
i*iif*»iii
(Report Continuid)
111-30
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESDL
STUDY NO, 5221.Oi
SPRAGlie-BAULEY RATS
Tabulated Animal Data
PROJECT 10: QCRESOL GROUP: 50 ME/KB SEX; FEHALE MYSi ALL
3 FATES! ALL
ID, NO;
SKELETAL MUSCLE
LWER
3J5^ 3057 3058 3J5? 3640 3041 2Q62 3023 3064 3045
KIDNEY
«PHROPftTHY, CHRONIC
HINEJMLIMTKW
LWHOCmC INFILTiWTE
iffDRIWEPHROSIS
EP3TH, ffifPERPLASIA, PELVIS
(1)
(13
i
(1)
(»
BUDDEH
UTERUS
» * *
EYES
ii»**ttit*
CE1W1X
§ *
(Report
111-31
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESDL
STUDY NO, 5221,04
SPMGUE-MM.EY ftVFS
Tabulated Animal Data
PROJECT ID: OCSESQl GROUP: 50 N6/KS SEX: FEWLE MYS: ALL
WGE 4 FATES: ALL
ID. NO: 3m 3057 3058 3flS? 30<50 30«1 30
-------
PATHOLOGY ASSOCIATES, INC
smo-CREsoi
STUDY NO. 5221.04
SPW5K-MULEY RATS
Tabulated Animal Data
PROJECT ID: OCRESQL GROUP; 50 HG/KS SEX: FEmii MYS; ALL
mi 5 FATESs ALL
ANIHfll ID. NO: 3B44 3047 3048 304? 3370 307! 3072 3073 3fl74 3075
BRAIN **«»*iiiii
SCIATIC NSWE * * * * t i * * I »
SPINftl CORO * f i I i * » I i i
SINE MftRRDU * t i i t t i »
IWDIBIIWR LfflPH NODE ittittttit
TtffflUS i**lit!t»!
WNCREftS iifi«fi«»f
PITUITflRY '* i * *.» t » i t i
WRATWROIO
(Report Continued)
111-33
-------
PATHOLOGY ASSOCIATES, INC.
ORTKO-CRESOL
STUDY NO. 5221.04
SPIW61E-MULEY RATS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP: 50 HE/KG SEX: FttMLE DAYS: ALL
W6E I FATES: ALL
10. NO: 3844 304? 3040 384? 3070 3071 3G72 3073 3Q74 3075
TRACHtt I i i I * i i i i f
ESOPHAGUS * * * * * » * * * i
A0RBWL 61JND i f i i i i « i i *
HEART
COLON fill* iti ii
DUQOEMH *ii»**i*i§
FORiSTtMACH i i « I » * I I i *
6UWULAR STQWCH * * * * * * * » » »
SKIN i i « i I I t i i »
ELM) *»ti*t»i#*
(Reaort Coniinued)
111-34
-------
PATHOLOGY ASSOCIATES, INC.
OTO-CRtSOL
mm NO, 3221.04
SPRftGUE-DAULEY RATS
Tabulated Animal Data
PROJECT ID: OCRESQL 5ROUP; 50 H6/KS SEX; FEWLE DAYS; ALL
PAGE 7 FflTES: ALL
ID, NO: 3064 3067 3fla3 3049 3070 3071 3072 3073 3D74 397S
SKELETAL MUSCLE * * « * i * * * * «
SPLEEN *iiiiiiiii
KIDNEY N M N H N N
NEPHSOPATHf, CHRONIC 1 -------
MINERALIZATION <2) - - <13 - - - - - -
LWHOCYI1C INFILTI^TE <1) <3>
HYORONEPHi?OSlS 1 -
mimm ILAOOER .iijiiiiiii
TEfTES i*iii«,i»i»
PROSTATE § i i i j « i i I i
(WARY » § » * * * * i i i
UTERUS * » * » * * * * » *
EYES » * » » t i ii,»*
Continued)
111-35
-------
PATHOLOGY ASSOCIATES, INC.
HTHO-CRESDL
STUDY NO. 5221,01
ftvrs
Tabulated Animal Data
PROJECT ID: OCSBOL S80UP: 50 MS/KS SEX: FBttLE DAYS! AIL
PAGE 9 FATES: ALL
10. NO; 3J« 33^7 30^8 30^? 31170 3fl71 3072 3073 3074 3i?5
CERVIX t 't t i i i i i * i
(Report Continued!
111-36
-------
PATHOLOGY ASSOCIATES, INC.
OOTHO-CRESOL
STUDY NO. 3221.04
SPMGUE-DAyLEY MTS
Tabulated Animal Data
PROJECT ID: OC1ESOL GROUP: 50 HSXKG SEX; FWLE DAYS; All
MGE ? FATES! ALL
mmi ID. NO; m& mi im iw mn 2071 3072 2073 2074 3075
OTHER TISSUES (WD LESIONS;
(End tf Report)
111-37
-------
PATHOLOGY ASSOCIATES, ]NC.
QRTHO-CRESOL
STUDY-NO, 5221.Oi
SPRAGUE-WJLEY RATS
Tabulated Animal Data
ID; DCRESOL GROUP: 175NG/KS SEX: fMLE DAYS; ALL
PftGE 1 FATES: ALL
ID. NO: 2757 2958 2939 29 <2) <1> <1) <1> - <2> <2> (1)
MNCi?EAS NN NK NNNN
LYHPHOCYTIC INFILTRATE - - (1) -
CHRONIC-ACTIVE ..... <1) - .-- -
PITUlTAITf NNNHNNNNN'N
(Report Continued)
111-38
-------
PATHOLOGY ASSOCIATES, INC.
(FTHQ-CRESOl
STUDY NO. 5221,04
RATS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP; 175HB/KG SEX: fttLE MYS; ALL
PAGE 2 FATES: ALL
ANIMAL ID, NO: 2?57 2?5B 2?5? 2960 2961 2942 2?d3 29« 2945 2?6i
WYRQIO N N N
EPITHELIAL CYST - - (2) (1) (1) .<1) (1!
MRflTHYROlD NNNNNNNNNN
TRACHEA N N N N N N N N N
DILATION, 6LANDS . <2>
ESOPlttGUS NNNNNNNNNN
»R£NAL 8lJ«0 H N N H N M - N
ECTASIA, HEDULW 2 - 2 - - - 2
LUN6
LTHPHOcmc !NFIL™TE,FERIV <2> <2> o> (2)
1NFLW, IMTERSTJTWL CHRONIC - - (1) U> - - - <2> (2) <1)
OSSEOUS HEWUSIft - <1) - - <2) <1> <3)
AORTA NNNNNNNNNN
COLON N N H N N N N N N N
(Report Continued)
111-39
-------
PATHOLOGY ASSOCIATES, INC.
(RTBQ-CRESQl
STUDY NO, 5221.04
SPJWGUE-IMUIE? RATS
Tabulated Animal Data
PROJECT 10; OCRESOL SRQOP: 17S1G/KG S£Xi MALE
PrtCE 3 FATES: fill
DAYS: ALL
HJOOEN*
ID. NO:
2957 2?58 295? 29dO 2?61 29d2 29(53 2964 2945 2U&
NNNNNNNNNN
FORESTQWCH
NNNNNNNNNN
NNNNNNNNNN
SKIN
NNNNNNNNNN
NftMfcRY
NNUNNNN
NN
SKELETAL MUSCLE
NNNNNNNNNN
LMR
IMFARCT, CAUDATE LDIE
LYMPHOCYTIC INFILTRATE
N .NNNNNNN
- • 4
<1)
HEMOSIDEROSIS
NMNNNNNH
11
MONEY
NEPHROPATHY, CHiDNIC
LYHPHOCYT1C INFILTRATE
-1-21
<$> - (1) - -
2111
(Report Continued)
III-40
-------
PATHOLOQY ASSOCIATES, INC.
GRTHD-CRESOL
STUOY MO, 5221.Oi
SPWGUE-MULFY WTS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP; 1? <2) (3) - - - <1) <2>
-------
PATHOLOGY ASSOCIATES, INC,
fliTHC-CRISCL
STUOY NO. 5221,04
WTS
Tabulated Animal Data
PROJECT IDs OCRESOL SROUP; 175K6/K6 SEX; 1*L£ DAYS; AH
PAK 5 FATES: ALL
flUNW. ID. NO; 2557 2?58 2959 29iO 29^1 2?42 2943
UTHER TISSUES WO LESKWSi
(Report
111-42
-------
PATHOLOGY ASSOCIATES, INC.
8TO-CRESOL
STUDY NO, 522S,Oi$
, SPRAGUE-MULEY RATS
Tabulated Animal Data
PROJECT 10i QCRESOL GROUP: 175HG/K6 SEX; mil DAYS; ALL
PAGE 4 FATES; ALL.
ID. NO; IW 29W 2919 2J78 2?7! 2572 2973 2974 2975 2976
BRAIN HNNNNNNNNN
SCIATIC NERVE • NNNNNNNNNM
mm. cosa) NNMNNNNNNN
iONE NNNNNNNNMH
BONE mRftOU NNNNNHNHNN
SWND NNNN'NNNNN
LYHPHOCYT3C INFILTRATE ,....,...
LtHPH NOOi ' N N N N H
LYMPHOID KYPERPLAS1A 23J----I2-
THYHUS N N
B10RRKA5E, flCUTE <1) (I) (!)
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STOY NO, 522J.06
SPfWGUE-WJLEY SATS
Tabulated Animal Data
PROJECT ID; QCRESOL GROUP: 1731S/KS SEX: WLE CAYS: ALL
»G£ ? FATES: ALL
mmi ID, NO: in? im iw 29?o 2971 2m im im 2??s mi
THYROID H N N N H N
EPITHELIAL CYST - (i) <2> £i) (2)
LWHOCYTIC INFILTRATE U) -------
PAMTKfROID NNNNNHNNNN
TMCHEfl NNNNNNNN
LTHPHOCYTJC INFILTRATE
NNNNNHNNH
sum N N KM N N
ECTASIA, MEDULLA 1 - i - t - - 2
LUN6 N
LWHOCYTIC INFILTRATE,PERM <2> <2> <2) <2> (I) <3> <2)
1NFW1, 1NTERST1TWL CHRONIC <1) <1) <2) - - <1) (!) <2>
HICTJOCYTDSIS ----
HB«T N N N
INFLATION, CHRONIC <1> (I) (2) <2> <1> - <2> (1)
AORTft HNNNNHNHNN
COLON N N N N N N N N " N • N
CRepuft Continued)
111-44
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221,OS
. • SPRAGUE-DflMlEY RATS
Tabulated Animal Data
WOJECT ID; OCRESOL GROUP: 173ia/KB SEX: WLE MYS; AIL
PrtSE 8 FATES; All
flNIMAL ID. NO; mi 2948 296? 2970 2971 2??2 2P73 2??4 2?75 2976
NHNNNHNNNN
FSI8ESTOWCH NHNNNHNNNH
HHNNNKNNNN
SKIN NHNNHHNNHH
SKELETAL MUSCLE NNNNNHNNNK
LIViR N N N H H N N
INFWfWTION, CHRONIC <1> <1> .-
WLCULUS - - - - 2 - i - - -
Cisport Continujd)
111-45
-------
PATHOLOGY ASSOCIATES, INC
ORTHfl-CiESOL
STUDY NO. 52?!. U
SPRAGUE-MULEY MT3
Tabulated Animal Data
PROJECT IDs OCRESOl 6ROUP; 175N6/KG SEX: IW.E DAYS; ALL
PftGE 9 FATiS: ALL
IB. HO: 2967 2?AS 2969 2970 297! 2972 2973 2?74 2975 297i
TESTES NNNNNNNNNN
PROSTATE N N N N N N N
LYMPHOCYTIC INFILTRATE <2> - - <1>
EYES NNNNN NNNN
mimi ATROPHY - - - - 2
(Report Continued)
111-46
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESCL
STUDY NO, 5221.04
SPRAGUE-WJLEY iMTS
Tabulated Animal Data
PROJECT ID: QCRESDL SROUPi 1?»G/KS SEX: MALE DAYS; ALL
WOE 10 FATES; AU
ID, NO: 2947 2941 2949 2970 2971 2972 2?73 2974 2??5 297^
OTHER TISSUES AND LESIIHS:
HESENTERY-FAT NECROSIS - ..... (2)
oi Riport)
111-47
-------
PATHOLOGY ASSOCIATES, INC.
QSTHO-CRiSOL
STUDY HO, 5221.04
SPRASUE-P4CT RATS
Tabulated Animal Data
PROJECT ID; OCRESQL GROUP', 175HG/KG SEX: FEWLE MYS; All
W6E 1 FATES; ALL
ID. MO; 3(JB9 30?0 3091 3052 30?3 3094 3093 SD9* 3fl?7 3091
BftUN • HNNNNNNNNN
SCIATIC NERUE NNNHNNHNNN
SPIJWL CORD NNNNNNNMNN
eQNE NNNNHNNNNN
BCf.I mRROU NHNNNNNNNN
SALIVARY SUHD N H N M H N N H.N N
WNDIBULAR LYMPH NODE N N H
LYMPH01D HYPERPLAS1A 3-22-1 t - 2 1
THYHUS N H N
HEMORRHAGE, ACUTE <2> {]> <» (1) - (!) - - (1)
PflNCREAS NHNNN . N. N N N
LWHOCYT1C INFILTiflTE - - - - - CD -
P1TU1TAIY NNNNNNNMHN
(Report Continued)
III-48
-------
PATHOLOGY ASSOCIATES, INC.
GR7HO-CFESOL
STUDY NO, 5221.Oi
SPRAGUE-WULEr RftTS
Tabulated Animal Data
PROJECT 1C: UCRESCL BROUP: 175MG/K6 SEX; F&WLE MYS; All
MBE 2 FATES; ALL
J&. NO: 308? 3090 30*1 30?2 3093 3094 3095 3094 3597 30?8
THfROlQ N N N N N N
EPIMLML CYST - - <2>
WM1HYROID ONNHNNNUUN
1RACHK NNHNNNNNN
LWKQCYT1C INFiLTWTE <1>
BOPWSUS NNNNNNNNNM
ADRBWL iLWD N N N N N N
ICTAS1A, HEDULW - 1 - 1 I 1 - - - -
LUNS
LWHOCYTIC )NFlLTWTE,PIRiy <2> <]> <3> <2) (5) <2> <1> (2> <2) <2>
1HFW1, INTERfTITWl CHRONIC - - <2> - - <1> - - <1>
Hisriocrrosis
HEART N N N N H N N
INFltftWlCN, CHRONIC - --(!)-
-------
PATHOLOGY ASSOCIATES, INC.
GRTHQ-CRESOL
mm NO, 5221.04
SPSAGUE-OftULEY 1WTS
Tabulated Animal Data
PROJECT 10: OCRcSOL ORQUP: 175HQ/KS SEX; FBtfLE MYS; ALL
PAGE 3 FATES: flU.
DUODENUM
ID. NO:
30B9 3fl?0 3891 30?2 3Q?3 309^ 30?5 30?4 30f7 3fl?8
HNHNNNNHNN
NNNNHNNNNN
GUWDUWR JTOHflCH
HNNNNNNNNH
SKIN
KNNNNNMNNN
NNNNNNKNNH
SKELETAL
HNNNNNNHHH
LIVE!
NNNNNNNNHH
SPLEEN
HBIOSIDEiOSIS
N N H N N
2212
KIDNEY
NEPHRflMTHY, CHRCNIC
LWHOCYTIC INFKWTE
HYORONEPHROSIS
N N N N N N N
- - 1 ------ 2
......
-------
PATHOLOGY ASSOCIATES, INC,
ORTHOCRESOl
STUDY NO. 5221.04
SP8AGUE-MULEY RATS
Tabulated Animal Data
PROJECT JO: OCRESOL CROUP; 175MG/KG SEX; FTOIE MYSi flU
PASE 4 FATES; ALL
ID, NO; 3089 30fS 30JS W2 33J3 3094 3SJ5 3fl?6 309? 3fl?8
QWRY NNNNNNHNNH
UTERUS NNNNN-NHNNN
EYES HNNNNNNNNN
CERVIX NNNNNNNNHN
(Report Caatinued)
111-51
-------
PATHOLOGY ASSOCIATES, INC
OffTHfl-CRESDL
STUDY NO, 5221,04
SPfWGUE-WLEY SATS
Tabulated Animal Data
PROJECT ID: UCRESCl GROUP; I731G/KG SEX; FEMALE DAYS: ALL
PAGE 5 FATES; ALL
i ID. NO: 3089 30fO 3fl?i 3392 38?3 30?4 30?5 3fl?6 30?? 3098
OTHER TISSUES AND LEillNS:
(Rspcrt Continued)
111-52 '
-------
PATHOLOGY ASSOCIATES, INC,
Qra-CRESOL
STUDY NO, 522S.04
SPMUE-MULEY RATS
Tabulated Animal Data
PROJECT 10: OCRESOL GROUP; I75MG/K6 SEX; FEWLE CttYS: ALL
W6E i FfflES; flU.
WIMflL ID, NO: •' 3099 3100 3101 3102 3103 3184 3103 3106 3107 31D8
«M1H NNNNNNNNNN
SCIATIC NEWE NNNNNNNNNN
SPIfttL CURD NNNNNNNNHN
BINE • NNNNNNNNNH
mi HARROU NNNNNNNNNxN
fiWND NNN.NMNNMNN
LWHNODi N N
LWHOIO HfPERPlASW 312-2222-1
TKtWUS
HEHORRW6E, ACUTE (2) <1> <2) <2) <1> <2)
CYST ----
JWCREAS N N N N N N N
LYMPHOCYTIC INFILTRATE CD
ttlWR ATROPHf (1) ---
PITUITARY NNN NNNN'NN
CfST ---
-------
PATHOLOGY ASSOCIATES, INC
DRTHfl-CRESOL •
STUDY NO. 5221.04
SPRAGUE-OAULEY RATS
Tabulated Animal Data
PROJECT ID; OCRESOL GROUP: 1731S/XS SEXi FTOLE DAYS: ALL
mi 7 FATES; ALL
ANIMAL ID. NO: 30?? 3100 3101 31(12 3103 3204 3105 3104 310? 3108
THYROID M , H N
EPITHELIAL CYST <2> - <2> <25 (2) - - <1)
LWPHOCYTIC INFILTRATE <2>
WlMTKYROIB NN^NNNNNNUH
TWCHEA NNNNNNN NN
LYMPHOCYT1C INFILTRATE ------- <2)
NNHNNNNHNH
«Ri«L 6LAND NHN NNNN
, MIDU11A ...]....
IUN8
LYMfHOCTTIC INFILTRATE,PERW <2> <2> <1> <1) <1)
INFLAH, INTERSTITIAL CHION1C <2> <1> CD
H1ST1QCYTQSIS - - - - (1) ----<»
NNNNNNHNNN
NNNNNHN.NNH
COLON NNNNNNNN,NN
(Report Ccntinuid)
ni-54
-------
PATHOLOGY ASSOCIATES, INC.
ORTIIO-CRESOL
STUDY NO, 5221.04
SPWSUE-WAEY RATS
Tabulated Animal Data
PROJECT ID: SJCRESOL SRBUPi 173HG/KG SEX; FEWIE MYS; AIL
PflCE 8 FflTES; ALL
DUQDENUN
ID. NC:
30?? 31GO 3101 3102 3403 311H 3105 3!0d 3107 3108
NNNNNNNNHN
FORESTCHACH
CCNSESTION
NHNNN NNNK
..... 1
wsi'wo STUWCH
NNNNNNHNNN
SKIN
NHNNNNHNNH
FWtttRY GLA.D
NNNNNNNNNK
SKELETftL MUSCLE
NNHNNNHNNN
LIUER
1NFL^*«TION1 CHION1C
LWPHOCfTIC INFILTRATE
N N N N N N N
- - -
SPLEEN.
HEH051DEROS1S
KIDNEY
NEPHRQPATHY, CHRONIC
MINERALIZATION
LYMPHOCYTIC ]NFlLlRftTE
N N
-------
PATHOLOGY ASSOCIATES, INC.
OCTHO-CRESOl
STUDY NO. 5221.06
SPIWSUE-MULEY BATS
Tabulated Animal Data
PROJECT ID: OCRESOL fiRQU?: 175MG/KG SEXi FTOLE DAYS: ALL
MGE 9 FATES: ALL " • '.
ID. NO; 30?? 3100 3101 3102 M03 3!Q4 3iQ5 3S04 310? 3J08
mimm BLADDER NNNNNNNHN
WFWrtttTIDN, ACUTE
-------
PATHOLOGY ASSOCIATES, INC.
ORTKO-CRESQL
STtiW NO, 5221.OS
SP5WGUE-DAULEY RATS
Tabulated Animal Data
PROJECT IB: QGRESBL IROUP; 1731G/X6 SEX; FEWLE DAYS: ALL
WEE 10 FATES; All
ffUMAL JD. NO: 30?? 310(1 31D1 3102 3103 3104 3105 3104 3107 3108
OTHER TISSUES (W LESItNS;
(End of Report)
111-57
-------
PATHOLOGY ASSOCIATES, INC.
OSTM-CR1SQL
STUDY NO, 5221,06
SPMGUE-MULEY SATS
Tabulated Animal Data
PROJECT ID; OMESOL GSOUPi ^OHE/KG SEX: MALE DAYS: ALL
WGE I FATES: ALL
flNIHAL ID. NO; 29S4 2990 2991 2992 2973 2994 2995 2994 299? 2991
ifWIN NNNNNNNNNN
SCIATIC NERVE NNNNNNNNNN
SPtfttL CORD NNNNNNNNNN
WNE HNNNNNHHNN
BONE HARROU NHNNNNNNNN
GLAND HNNNUNNNNH
LYHPH NUDE N U N N
CON5EJT10N 3 ---------
LYMPHQII HYPESPLAS1A J 2 - 2 ! 1
THWUS N A
HMOWWGE, ACUTE - <1) <2)
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOl
STUDY HO. 5221.04
SPRAGUE-MUIEY RATS
Tabulated Animal Data
PROJECT ID: OCRESQL SROUP: ^BOMB/KG SEX: mil MYS: ALL
PAGE 2 FATES: ALL
(WHAL ID. NO:
THYROID
EPITHELIAL CTST
LYMPHOCYTIC INFILTRATE
2W 299D 2991 2992 2993 2594 29?5 2994 2997 2993
(2)
' (!)
(1)
N N
<2)
<2>
PARATHYROID
NNNUNNNNNN
TRACHEA
LWPHOCYTIC INFILTRATE
N N N NNNNNN
<1) ......
ESOPHAGUS
INFLAM1AT10N, CHRONIC
NH H N N N N N
(])
<3>
<1)
<»
22
(2) (31
- <2)
<2>
(2) <2) <2>
-3-
- 131
<2>
ffiART
INFLAltWTIDN, CHRONIC
N N N N N N H
- (1)
(Report Continued)
111-59
-------
PATHOLOGY ASSOCIATES, INC.
QRTHO-CRESOL
STUDY NO, 5221.OS
SPRAGUE-OAULEf RATS
Tabulated Animal Data
PROJECT 10: OCRESOL GROUP; 400MS/K8 SEX: miE DAYS: ALL
PAGE 3 FATES: AH
ANIMAL ID. NO: 2984 2990 mi im 2m 2m im wt> 2m im
AORTA NNNNNNNNNN
COLON NNNNNNNNNN
TOENlfl NNNN.NNNNNN
FORESTOrMCH NNNNNNNNNM
6UMDUUK STDfttCH NNNNNNNNNN
SKIN NNNNNNNNNN
rm*WY SL^D NNNUNNNNUN
SKELETAL MUSCLE NNNNNNN-NNN
IMR N N N N N N N
CTOE5TICN 121 - - <2>
NECROSIS, CUMULATIVE ---
lYMPHOCYTIC INFILTRftlE
-------
PATHOLOGY ASSOCIATES, INC.
ORTHD-CRESOL
STUDY NO. 5221.04
SPWGUE-OAULEY EATS
Tabulated Animal Data
PROJECT ID: OCSESOl GROUP; dOONG/KG SEX: WLE MYS; AU
Ml 4 FATES: ALL
WML ID. NO: 2984 2??D 29?1 2??2 2993 2?94 29?5 Wt, 2?97 2998
KIDNEY N N N N N N K
NEPHROPATHY, CHRONIC I - - 1 1
URINARY BUDOER N N N N N N N
LWPHOCYTIC INFILTRATE - - (35
CALCULUS 2 1
TESTES NNNNNNNNN
ATROPHY, SEMINIFEROUS TU8ULE (1) ....
PROSTATE NN NNNNNNN
LYHPHOCYTIC IffflLTWTE - - <3>
NNNNNNNNNN
(Report Continued)
111-61
-------
PATHOLOGY ASSOCIATES, INC.
QRTHD-CRESQL
STUDY NO. 5221.04
SPRAGUE-MULEY RATS
Tabulated Animal Data
PROJECT ID; OCRESOL GROUP; iflflhG/KG SEX; mil DAYS: ALL
PAW 5 ftfllS: ALL
18. HO; 2J84 2»0 2W W?2 2J?3 2?f4 2??5 19U
OTHER TISSUES AND LESIWSi
(Report Centinued)
111-62
-------
PATHOLOGY ASSOCIATES, INC.
QRTKO-CRiSOL
STUDY NO. 5221.fli
SPRA6UI-WULEY IWS
Tabulated Animal Data
PROJECT ID: OCSESOL SROOP: ^OflMS/KS SEX; MLE • > OftYS; Ail.
PAGE j MTEi: ALL '• •'
(WimL ID. NO: 2999 3008 3001 3082 3Q03 3004 3035 300(S 3007 3008
NKNNHHNNNN
SCIATIC NEWE NNNNNNNNNN
SPIWL CCRO NMNNNNNNNN
8(WE HNNNNNNNNN
BONI WRROU ' NNNNHNNNNN
SALIVARY BUW NNNNNNNNNN
IWD1IUWR LWPH NODI N N N N H
CtKSESTION 2-3--
LYMPHOID (ffPERPLASIA 1 - - I - - 2
TOUUS
<2> <2> U> <1> <2> <2> <1) (3)
IWCSKS NNNHNNNfl N
LWPHOCYTIC INFJLTWTi '-
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 5221.Qd
SPRAGUE-BAULEY RATS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP; iOOMG/KG SEXi fWLE MYSi ALL
PAGE 7 FATES: All
MWL ID. NO: 2??? 3(100 3001 3002 3003 3004 3005 3004 3007 3008
THYROID N N N N AN
EPITHELIAL CYST - - - (2) - - <1) - - (U
IWHOCmC INFILTRATE <2>
INFUWfflGN, GRANULGWTOUS - - 3 .-.---.
WRATHYR010 HNNNNNNNNN
TRACHW NNNNN NANN
CONiESTION 2
INFLATION, ACUTE ----
iSQPHASUS NHKNHNMNNN
ADREWL GLAND NNN NNNNNN
ECTASIA, MEDULLA ... j ......
LUNfi
LWPHOCTTIC INFILTWTE.PERW <2) <2) <25 <25 <1) - <1> <3) <1>
1HFLAM, IffTEISTITIAL CHRONIC <]>-<»-
OIL ORDPLETS - 2 - - - 2 - 3 - I
C(W6EST1(W C31 - - [31 - [31 - <2>
EDEMA <2> - - <2) - <2> - <2>
HEMORRWGE -{[)- <2)
(Rjport Continutd)
in-64
-------
PATHOLOGY ASSOCIATES, INC.
GR7HO-CRESOL
STUDY NO, 3221.04
SPRAGUE-MULEY SATS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP: 400HG/KG SEX: WLE DAYS: All
PAGE 8 FflTES: ALL
AORTA
ID. NO:
25*79 30DQ 3001 3002 3083 3004 38B5 300^ 300? 3008
NHNNNNNNNN
COLON
NNNNNNNANN
DUODENIW
FORESTWCH
NNNNNANflNN
NNNNNNHNNN
STOWCH
D1WT1DN, 6LAND
NNNHNNH
SKIN
NNNKNNNNNH
SWND
NNNNNNHNNN
SKELETAL HUSCLE
NNNNNNNNNN
LIVER
CONSESTIflN
N NNNNNNNN
-2 ........
SPLEEN
HEHOSIOERDS1S
1 1 1 2 1
N N N N H
(Report Continued)
111-65
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESQL
STUDY NO, 5221.04
SPWtGUE-MULEY FMT5
Tabulated Animal Data
PROJECT ID! OCRESDL BRQUP; 6DOHG/KB SIX: mil WYSi All
? FATES: All
ID. NO;
KIDNEY
NEPHROMTHY, CHRONIC
2W 3030 3B01 3002 3003 30 M 3005 3D04 3007 3008
N N N N N N
i 1 1 I .....
URINARY IL/WDER
NNHMNNH NN
....... 2
TESTES
PROSTATE
NNMHNNNHNN
CD
N N
N N
EYES
CATAWCT,
NNNNNNNNN
(Report Continuid)
111-66
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRKOL
STUDY NO. 5221.0(5
SPRAGUE-MULEY HATS
Tabulated Animal Data
PROJECT 10; OCHESOl iROU?; 400MS/K3 SEX; «&E DAYS: ALL
W6E 10 FATES: flLL
(Him. ID, NO: 29?9 3000 3001 3002 3803 30D4 3005 3304 3007 3008
OTHER TISSUES (WO LESIONS:
(Report Cofttinytd)
111-67
-------
PATHOLOGY ASSOCIATES, INC,
08THQ-CRES3L
STUDY NO. 5221. IM
SPRft6UE-WWLFf RATS
Tabulated Animal Data
PROJECT ID; QCRESOL 6SOUP; AOOHS/KS SH: hftLE DAYS: ALL
PAGE 11 RTES; ALL
(WIHAL ID, NO: 300?
mm N
SCIATIC NERUE N
CORD N
IONE
ONE WtRRCU
SALIVARY
IWOliUWR LYMPH NODE
LWKDID HYPERPWSW
THYKUS
E, ACUTE
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESQL
STUDY NO. 5221.06
SPRASUE-WWLEY RATS
Tabulated Animal Data
PROJECT 10; OCRESQL SROUP; 400MG/KG SEXi WLE DAYS; ALL
flftCE 12 FATES: ALL
i IB. HO; 300?
PA1MTHYROID N
• N
ESOPMGUS
ADRENAL 5UWD
ICTASIA, MEDULLA
L1M
LYMPHDCYTIC INF1LTMTE,PER!M
HWRT
AORTA
COLON
DUODE34LH
FOREST'DWCH
BU5HDULAR
(Report Continued)
111-69
-------
PATHOLOGY ASSOCIATES, INC.
CRTHO-CRESOL
STUDY NO. 5221.04
SPRAGUE-DAULEY »TS
Tabulated Animal Data
PROJECT 10! OCRESDl SROUP; MOMS/KG SEX; MALE DAYS: ALL
PASS 13 FATEii fill
10. HO: 300?
SKIN N
U
MUiCL! K
LIVER
INFWWTJON, CHRCN1C
SPLEEN
KIDNEY
mmmm, CHRCNIC
URIfWRY BWDOER
TESTES
PROSTATE
EYES
CiJtitinusd)
111-70
-------
PATHOLOGY ASSOCIATES, INC.
OHTHC-CRESOL
STUDY NO, 5221,U
SPRAGiJE-DAULO' »TS
Tabulated Animal Data
PROJECT ID: OCRESOL CROP: WONG/KG SEX: MALE DAYS; ALL
WOE 14 ' FATES: ALL
ID, NO: 3009
OTHES TISSUES AND LESIINS:
(End of Sepcrt)
111-71
-------
PATHOLOGY ASSOCIATES, INC.
ORTHQ-CRESQl
STUDY NO. 5221.06
SPMGUE-fWJLEY IOTS
Tabulated Animal Data
PROJECT ID; QCRESOL GROUP: MOMG/KB SEX: FE»LE - DAYS: ALL
W6E 1 FATES; AH
ID. Nfl; 3112 3113 3121 3122 3123 3124 3125 3124 312? 3128
BRAIN NNNNNNNNNN
SCIATIC NERVE NNNNNNNNNN
SPINAL CORD UNNNNNNNNN
80NE NNNNNNNNNN
BCNE WRROy NNNNNNNNNN
6UWD NNNHNNNNNN
NWIBUWR LWH NOM N N
HEHORRtWGE, ACUTE - - - <2>. - - -
OW6EST1CN 2 ... 2 - - 2
LWHOID HYPEHPWSIA I 2 - 2 2 J
THfflUS N N N N
HEH08RIW6E, flCUTE <1> - - <1> <1) <2) - <2> -
MNCREAS NNNNNNNN- NN
PITUIWRY NNNNNNNNNN
(Report Continuetl)
111-72
-------
PATHOLOGY ASSOCIATES, INC.
CRTHO-CRISQl
STUDY NO. 5221.06
SP&GUE-DAULEY RATS
Tabulated Animal Data
PROJECT !D: OCRESOl SROUP-. MCHE/KG SEX: FEMALE MYSi ALL
PAGE 2 FATES; ALL
ID. NO: 3112 3113 3121 3122 3423 3124 3125 3!2A 3127 3128
THYROID N N N N H N
EPITHELIAL CYST (1) (1) - <2). <2)
OIL DROPLETS 322-22-231-
[33 - - [3J li: - - [31 13] [33
(2) - <2> <2) (1) <3> (2) (2) (!)
HBiORRWGE - - - <1> <1)
lACIERIfl <2) - -
HEART NNNNNNHNNN
AORTA NNNNNNNN'HN
(Riport
111-73
-------
PATHOLOGY ASSOCIATES, INC.
OETHO-CRESOL
STUDY NO. 5221.04
SPRAGUMMULEY MTS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP: 600HS/K5 SEX: FBW.E DAYS; ALL
PftGE 3 FATES: ALL
ANIMAL ID. NO:
COLON
3J22 3113 3123 3S22 3123 3124 3125 3124 312? 3128
NNNNNNNNNN
WJODEMJH
NN
NNNNNNN
FORESTGfttCH
NNNNNNNNNN
JWIOUWR STOW*
NNNNNNNNNN
SK]N
JWtWIW SLM)
SKELETAL MUSCLE
N N N N N N N N N N
NNUNNNNNUN
NNNNNNNNNK
LIVER
CCNGEiTiaN
NNNNNNN N
....... 2-2
SPL1EN •
HMSIOEROSIS
NANNNN NN
...... 2 - - 2
KIDNEY
NIFHiflPATHf, CHRONIC
INFLAmftTJDN, AWTE, PELMIS
CfST
NNN
NNN
NN
(Rfport Continued)
III-74
-------
PATHOLOGY ASSOCIATES, INC.
ORTKO-CRESOL
STUDY NO, 5221,M
SPMGUE-W4EY RATS
Tabulated Animal Data
PROJECT ID: OCRESQL iROUP; WOHG/HS SEX: FBttLE MYS: ALL
MOE 4 FATEi: AU
mmi ID. NO; 3112 3113 3121 3122 3123 3124 3125 3124 3127 3128
mmm BLADDER NNHNNIINHNH
WiRY NNNNNNNHNH
WESUS NNNNNNHNNN
EYES NHNNMNN NH
CATAIMCT, LENS 2
CERVIX NNNNHNNNNN
(Report Continu»dJ
111-75
-------
PATHOLOGY ASSOCIATES, INC.
1THO-CRESOL
STUDY NO, 5221,05
MTS
Tabulated Animal Data
PROJECT 15; CCRE30L 6ROUP: 4BCHS/K5 SEX; FEHM.E DAYS; ALL
PAGE 5 FATES; ALL
.(ttm. 10. NO:
OTHER TISSUES AND LESIINS:
HESENTERY-FAT NECROSIS
LAfflW-HEMORiWGE, ACUTE
JEJtMH-NOBW.
1LEUH-NORMAL
3112 3113 312S 3122 JI23 3124 312S 3124 3127 3123
(3)
(Report Continutd)
111-76
-------
PATHOLOGY ASSOCIATES, INC.
ORTHQ-CRESOL
STUDY NO. 5221.04
SPRAGUE-DMLEY RA7S
Tabulated Animal Data
PROJECT ID: QCfiESOL GROUP; iOW1S/K5 SEX: FEHALE OftYS: ALL
PASE 4 FATES: All
i 10, NO: 3129 3130 3131 3132 3133 3134 3133 3$3 <1> <2) <2) <1>
WWCREAS . NNANNAN NN
LYMPHOCYTIC INF1L1MTE (13 - -
PITUITARY N N N N N N N N,N N
(Repsri Continued!
111-77
-------
PATHOLOGY ASSOCIATES, INC.
ORTHQ-CRISQL
STUDY NO, 3221.06
SPWGd-MUlEY RATS
Tabulated Animal Data
ROJECT ID; OCRESOl SRCUP: iOOMG/KS SEX: FTOLE DAYS; AIL
WGE7 FATES! All
ANIWL 10. NO: 312? 3130 3131 3132 3-133 3134 3S35 3136 3137 3138
THYIOID N A N N N
EPITHELIAL CYST - <2> - (2)
LYMPHQCYTIC INFILTRATE U>
PARATHYROID NUUNUNNNNH
TRACHW NNNNNNKNNN
ESOPHAGUS NNNNNNNNN
, CHRCN1C ......... (2)
6LWD N NNNNNNNH
ECTftSW, HIOULLA 1 -..--..-
LUNS
L1WHOCYTIC 1NF3LTRATE,PE11V
IWfH, 1MTERSTITWL CHSDNIC <2> - <2)
OIL DROPLETS ' - - 3 (1) - 3 - - 2 2
C»GESTIQN C31 - <3> C31 <2> <2> - - <3) CIS
mm <2> - w <3> - <3) - - <2> <3>
HMRRHflEE (1! - - (1) - (1) - - - -
H1ST10CYTOSIS - - (2) - - ' -
FNEUHCNW, FDREI6N BUOY ---
PNEIMCNW, CHRONIC-rtCTlUE - - - <3)
NNNNNNN, NN
, CHRONIC <2> -
(Report Continuid)
111-78
-------
PATHOLOGY ASSOCIATES, INC
QKTHfKRESDL
STUDY NO, 5221,04
SPIWGUE-DAULEY RATS
Tabulated Animal Data
PROJECT ID: OCRESOL GROUP! iOOMG/KG SEX: FBttLE DAYS: ALL
mi 8 MIES: ALL
AORTA
ID. NO:
3129 3130 3131 3132 J133 3131 3135 3134 3137 313S
N N'N N N N N N N H
COLIN
NN
NN
NNNN
DUODENUM
NNANNANNAN
FCRESTWCH
NNNNNNNNNN
STWCH
NNNNNNNNNH
SKIN
NNNNNNNNNN
8WNO
SCILETALMUSCLI
NNNNN
NNNN
NMNNNNNNHN
L1VEI
OT6ESTIDN
LYHPHOCrriC INFILTRflTE
<1)
N NNNNNHH
1 .......
SPLEEN
HEHDSIDEROSIS
N N N N N N
2 2 - - - - i 2
-------
PATHOLOGY ASSOCIATES, INC
STUDY NO. 5221.04
SPRAGUE-MULDf RATS
Tabulated Animal Data
PROJECT ID: OCRESOL 8ROUP; fl>OM8/K6 SEX; FEMALE DAYS: ALL
PAGE 9 FATES j AU
L ID. NO:
KIDNEY
NiPHRQPATHY, CHRONIC
HTDRCNEPHiOSIS
3129 3130 3131 3132 1133 3134 3135 3!34 3137 313B
1 1
N N N A H
URIfWTf BWOOIR
NNNNNNNNMN
DWRY
NNNNNNNNMN
UTERUS
NNHNNNNNNN
EYES
NNHNNNNNNN
CERVIX
NNNNNNNNNN
(Report Continued)
111-80
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CESOl
STU9YNC. 5221,06
SPfWSUE-OAULEY RATS
Tabulated Animal Data
PROJECT IDi CCRE50L GROUP: 40W6/KO SEX: FEMLE DSYS: SLL
ME 10 FftTES: ALL
ID. NO: 31251 3130 3131 3132 3133 3134 3135 3134 3137 3138
OTHER TISSUES AND LES1WS:
111-81
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESQl
STUOY NO. 5221.U
SPRAGUE-MULEY RATS
Tabulated Animal Data
JEn ID: QCRESOL BRQUP: dflONS/K6 SEX; FEmiE DAYS: ALL
M3E 11 FATES; ALL
ftNIHAL ID. NO; 313? 3140 314!
BRAIN N N y
SCIATIC NEWE N N H
SPIWL CORD ' N N N
BONE N N N
BONE WRROU N N N
SAL I WRY GLAND N N N
(WTOJBUWR LYMPH NODE H A
LfHPHOJD HYPERPLASIfl 3
1WMUS ft
HEWORRM6E, ACUTE
-------
PATHOLOGY ASSOCIATES, INC.
OR1HO-CRESOL
STUDY NO. 5221,OJ
SPRASUE-MULEY SATS
Tabulated Animal Data
PROJECT ID; DCRESOL SROUP:'400HG/KS SEX: Fimi£ DAYS: ALL
FATES: ALL
ANIttfl ID, NO: 3139 3140 3141
TKYROiD N
EPITHELIAL CYST <2> - (13
LYMPHOCYTE llfflLTMTE (1)
K N H
TRACHEA N N N
ESOPWGUS H N H
BLANO H H A
L1M
LYMPHKYTIC INFILTRATE,PIR1V <1> «) <2)
1NFLAM, 1NHRST1TIAL CHRONIC <1> <2> <2>
OIL DMPLETS - 1 2
CDNBESTltW - (3)
EDBtt - <2) <2>
HlfTIQCHOSIS - (1) -
WEIWDNW, CHRONIC-ACTM - - <2>
HiW N N N
AORTA N N H
COLON N N H
{Report Continued)
111-83
-------
PATHOLOGY ASSOCIATES, INC,
ORTHO-CRISQL
STUDY NO, 5221.06
SPRftGUE-MULEY MTS
Tabulated Animal Data.
PROJECT ID: OCRESGL BROUP; iOCHQ/KS SEX: FEWLE DAYS! ALL
PAGE 13 FATES: ALL
KJOOENIH
ID, NO:
3139 3140 31 «
N N N
FQRESTOWCH
N N N
SUW1JWR .STITCH
N N N
SKIN
N N N
8UWO
MUSCLE
N N N
« H N
LIVER
N N N
SPLEBi
HHDSIDERSJSIS
KIDNEY
ffiPHROPATffif, CHRONIC
HYDRONEPHROSIS
BWDDER
N U U
mm
(Report Confinutd)
111-84
-------
PATHOLOGY ASSOCIATES, INC.
ORTHB-CRESOL
STUDY NO, 5221.06
SPRAGUE-WJLFf RATS
Tabulated Animal Data
PROJECT 10: OCRESOL 6ROUP: ^OOHG/KG SEX: FEmiE MYS; AIL
PfiGE 14 FATES; fill
ID. NO; 3139 3140 3141
UTERUS N N K
EYES N N N
CERVIX N N N
ContinytdJ
111-85
-------
PATHOLOGY ASSOCIATES, INC.
OiTHO-CRESOL
STUPY NO, 5221. Oi
RATS
Tabulated Animal Data
PROJECT ID; QCRESOL GROUP; 4flDHi/K6 SEX; WHLE MYS; AH
MGE 15 FATES; ALL
ID. NO: 313? 3NO 3HI
OTHER TISSUES AND LESIINS:
(End ri Report)
III-8S
-------
IV, GROSS VS. MICROSCOPIC FINDINGS
-------
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY MO, 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Finding-
PROJECT ID: OCRE30L GROUP; Q.OMG/KG SEX: MALE DAYS: ALL
PAGE 1 , FATES: ALL
ANIMAL NO; 2391 PATHOLOGY ID. NO: 852891 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2892 PATHOLOGY ID, NO: 852892 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
..cFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NSL
> LARGE HAIR WITH ASSOCIATED
INFLAMMATION IN MAJOR BRONCHIOLE
ANIMAL NO: 2893 PATHOLOGY ID. NO: 852893 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 5221 ,Q6
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL " GROUP: O.QMG/KG SEX: MALE DAYS: ALL
PAGE 2 FATES; ALL
ANIMAL NO: 2394 PATHOLOGY ID, NO: 852S94 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHOLQSY;
>SPLEEN-CYST ALONG MARGIN-CLEAR, ' SPLEEN- CYST
3X2MM
>KIDNEY~SLIGHTLY MOTTLED AND PITTED NO COROLLARY CHANGE DETECTED
ANIMAL NO; 2895 PATHOLOGY ID. NO5 852895 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
ROBABLE CAUSE OF DEATH: DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGYi
>NGL
ANIMAL NO: 2896 PATHOLOGY ID. NO: 852896 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH-: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO, 5221 .06
SPRAGUE-DAULEY RATS
Correlation o-f Gross. &c Micro Findings
PROJECT ID: OCRESOL CROUP: O.OMG/KG SEX: MALE DAYS: ALL
PAGE 3 FATES: ALL
ANIMAL NO: 289? PATHOLOGY ID. NO: 852897 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST; 9\
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY: '
>NGL
ANIMAL NO: 2398 PATHOLOGY ID. NO: 352898 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
/NQL
ANIMAL NO: 2899 PATHOLOGY ID. NO: 852899 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: , RELATED HISTOPATHOLOGY5
>MESENTERIC FAT-i OX3MM) ROUND DARK MESENTERIC LN-HEMORRHAGE
NODULE.
>LIYER-MOTTLED LIVER- NECROSIS, GQAGULATIUE; LIVER "
LESION COMPATIBLE WITH FOCAL
ISCHEMIA. NO ETIOLOGICAL AGENT
NOTED.
(Report Continued)
IV-3
-------
PATHOLOGY ASSOCIATES, INC.
QRTHO-CRESQL
STUDY NO. 5221. Q*
SPRAGUE-DAUILEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP: Q.OMG/KG SEX: MALE DAYS; ALL
PAGE 4 FATES: ALL
ANIMAL NO: 2900 PATHOLOGY ID, NO: 852900 PATHOLOGIST; DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST; 9i
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>INGUINAL LYMPH NODE-RIGHT ING. LN-LYMPHOID HYPERPLASIA
ENLARGEDCUITH MAMMARY TISSUE)
ANIMAL NO; 2901 PATHOLOGY ID. NO; 852901 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TESTt 93
EFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2902 PATHOLOGY ID. NO.- 852902 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2903 PATHOLOGY ID. NO: 852903 •'' PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATHs DAYS ON TEST: 9c
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHQLOGY:
>NGL
(Report Continued)
IV-4-
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation of Gross & Micro Findings
PROJECT ID: OCRESOL " GROUP: 0.OHG/KG SEX: MALE DAYS: ALL
PAGE 5 FATES; ALL
ANIMAL NO: 2904 PATHOLOGY ID. NO: 852904 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO:'2905 PATHOLOGY ID. NO: 852905 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
,-JGL
ANIMAL NO: 2906 PATHOLOGY ID. NO: 852906 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>MGL
ANIMAL NO: 2907 PATHOLOGY ID. NO: 852907 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH.- DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
IV-5
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO, 5221 ,Q6
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRE30L " GROUP: 0.QMG/KG SEX: MALE DAYS: ALL
PAGE 6 FATES! ALL
ANIMAL NO: 2908 PATHOLOGY ID. NO: 852908 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH 5 DAYS ON TEST; 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2?Q9 PATHOLOGY ID. NO: 852P09 PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
ANIMAL NO: 2910 PATHOLOGY ID. NO: 852910 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED.HISTOPATHOLOGY:
>NGL
-------
PATHOLHGY ASSOCIATES, INC
QRTHO-CRESQL
STUDY NO. 5221.04
SPRAQUE-OAU1LEY RATS-
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP: O.OMG/KG SEX: FEMALE DAYS: ALL
PAGE 1 FATES 5 ALL
ANIMAL MO: 3023 PATHOLOGY ID. NO: 353023 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOL08Y:
>MGL
ANIMAL NO: 3024 PATHOLOGY ID. NO: 853024 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
iFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3025 PATHOLOGY ID. NO: 853025 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: - DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 302<5 PATHOLOGY ID. NOs 853026 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: • RELATED HISTOPATHOL06Y:
>NGL
IV-7
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 5221 .06
SPRAGUE-QAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL . GROUP: Q.OMG/KG SEX: FEMALE DAYS! ALL
PAGE 2 " FATES: ALL
ANIMAL NO; 3027 PATHOLOGY ID, NO; 853027 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>HISTO-KIDNEY-i C1X1MM) CYST IN NO COROLLARY CHAN6E DETECTED
CORTEX OF RT. KIDNEY.
ANIMAL NO: 3028 PATHOLOGY ID. NO: 853028 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
ANIMAL NO: 3029 PATHOLOGY ID. NOi 85302? PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3030 PATHOLOGY ID. NO: 853030 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
IV-8
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221 .06
SPRAGUE-DAWLEY RATS
Correlation of Gross &'Micro Findings
PROJECT ID; OCRESOL GROUP; O.OMG/KG SEX: FEMALE DAYS: ALL
PAGE 3 - FATES: ALL
ANIMAL NO; 3031 PATHOLOGY ID. NO: 853031 PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD; RELATED HI3TOPATHOLOGY:
>NGL
ANIHAL NO: 3032 PATHOLOGY ID, NO; 853032 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY;
NGL
ANIMAL NO: 3033 PATHOLOGY ID. NO: 853033 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: . DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY;
>HISTO-AZGOS AND RT. DIAPHRAGMATIC POORLY PERFUSED WITH BLOOD.
LUNG PALE IN COLOR.
ANIMAL NO: 3034 PATHOLOGY ID. NO: 853034 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: • RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
IV-9
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL / GROUP: 0,QMS/KG SEX: FEMALE DAYS: ALL
PAGE 4 " FATES; ALL
ANIMAL NO: 3035 • PATHOLOGY ID. NO: 853035 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ' " DAYS CM TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>H!STQ-RT. KIDNEY-DILATED PELUIS. KIDNEY- HYDRONEPHROSIS
ANIMAL NO; 3036 PATHOLOGY ID. NO: 853036 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
-PROBABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGYt
NGL
ANIMAL NO; 3037 PATHOLOGY ID, NOs 853037 PATHOLOGIST! DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO-NECROPSY RECORD: RELATED HISTOPATHOLOGY;
)NGL
ANIMAL NO: 3038 PATHOLOGY ID. NO: 853038 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: -; DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
IV-10
-------
PATHOLOGY ASSOCIATES, INC.
QRTHQ-CRE30L
STUDY NO. 5221.06
SPP.AGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP: 0.OMG/KG SEX: FEMALE DAYS: ALL
PAGE 5 -" FATES: ALL
ANIMAL NO: 3039 PATHOLOGY ID. NO: 853039 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: • DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD! RELATED HISTOPATHQLQGY:
>HI£TO-RT. KIDNEY-DILATED PELVIS. KIDNEY- HYDRONEPHROSIS
>HISTO-CALCIFIED MATERIAL FOUND IN NO COROLLARY CHANCE DETECTED
BLADDER.
ANIMAL NO: 3040 PATHOLOGY 10. NO: 853040 PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST-. 93
. EFERENCE T0 NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3041 PATHOLOGY ID. NO: 853041 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST'. 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHDLOGY:
>NGL
(Report Continued)
IV-11
-------
ORTHO-CRE30L
STUDY NO. 5221,06
SPRAGUE-OAWLEY RATS
Correlation of Gross & Micro Findings
PROJECT ID; OCRESOL GROUP: O.OMG/KG SEX: FEMALE DAYS: ALL
PAGE 6 - FATES: ALL
ANIMAL NO: 3042 • PATHOLOGY 10. NO: 853042 PATHOLOGIST! DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLQGY;
>NGL
(End o-f Riport)
IV-12
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP: 50 MS. KG - 'SEX: MALE DAYS: ALL
PACE 1 • FATES: ALL
ANIMAL NO: 2924 PATHOLOGY ID. NO: 852924 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>KIDNEY-SLIGHTLY MOTTLED. NO COROLLARY CHANGE DETECTED
ANIMAL NQ5 2925 PATHOLOGY ID, NO: 852925 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
.EFERENCE TO NECROPSY RECORDS RELATED HISTOPATHOLOGY5
>NGL
ANIMAL NO: 2926 ' PATHOLOGY ID. NO: 852926 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL MO: 2927 PATHOLOGY ID. NO: 852927 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
1V-13
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO, 5221 ,06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL • GROUP: 50 MG.KG SEX: MALE DAYSj ALL
PAGE 2 FATES: ALL
ANIMAL NO: 2928 PATHOLOGY ID. NO: 85,2923 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGYi
>NGL
ANIMAL NO: 2929 PATHOLOGY ID, NO: 85292? PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
y
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHQLQGY:
_T. KIDNEY-PELVIS DILATED, KIDNEY- HYDRONEPHROSIS
ANIMAL NO: 293G PATHOLOGY ID. NO: 852930 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGYs
>KIDNEYS-SL!GHTLY MOTTLED. NO COROLLARY CHANGE DETECTED
>TESTES-SMALL TESTES- ATROPHY, SEMINIFEROUS TUBULE
ANIMAL NO: 2931 PATHOLOGY ID. NO: 852931 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>KIDMEYS-SLIGHTLY MOTTLED AND PITTED. KIDNEY- NEPHROPATHY, CHRONIC
IV-14
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC.
QRTHQ-CRESQL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID; OCRESOL - GROUP; 50 MS.KG SEX: MALE DAYS: ALL
PAGE 3 FATES: ALL
ANIMAL NO; 2932 PATHOLOGY ID, NO: 852932 PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; • DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NQL
ANIMAL NO: 2933 . PATHOLOGY ID, NO: 852933 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
ANIMAL NO: 2934 PATHOLOGY ID. NO: 852934 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: - DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD! RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO; 2935 PATHOLOGY ID. NO: 852935 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY;
>NGL
IV-15
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC,
ORTHO-CRESQL
STUDY NO. 5221.06
3PRAGUE-DAUILEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL - GROUP: 50 MG.KG SEX: MALE DAYS: ALL
PAGE 4 ' FATES! ALL
ANIMAL NO; 2936 PATHOLOGY ID, NO: 352936 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2937 PATHOLOGY ID. NOt 352937 PATHOLOGIST! DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
ANIMAL NO: 2938 PATHOLOGY ID. NO: 852938 PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL MO: 2939 PATHOLOGY ID. NO: 852939 PATHOLOGIST? DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
IV-16
-------
PATHOLOGY ASSOUiA'l ES , AINU.
ORTHO-CRESOL.
STUDY NO. 5221,06
SPRAGUE-OAWLEY RATS
Correlation o-f Gross &• Micro Findings.
PROJECT ID; OCRESOL GROUP: 50 MG.KG SEX: MALE DAYS: ALL
PAGE 5 ' FATES; ALL
ANIMAL NO: 2940 PATHOLOGY ID. NO: 352940 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO; 2941 PATHOLOGY ID. NO: 852941 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST; 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
ANIMAL NO: 2942 PATHOLOGY ID. NO: 852942 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2943 PATHOLOGY ID, NO: 852943 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(End o-f Report)
IV-17
-------
PATHOLOGY ASSOCIATES, INC.
QRTHO-CRESOL
STUDY NO.' 5221 .06
SPRAGUE-OAULEY RATS
Correlation of Gross & Micro Findings
PROJECT ID; OCRESOL GROUP: 50 MG/KG SEXr FEMALE DAYS: ALL
PAGE i FATES: ALL
ANIMAL NO: 3054 PATHOLOGY ID. NO: 353056 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91,
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3057 . PATHOLOGY ID. NO: 853057 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST 5 92
;EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3058 PATHOLOGY ID. NO: 853058 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3059 PATHOLOGY ID. NO! 853059 ' PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
IV-18
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESQL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT 10: OCRESOL GROUP: 50 MG/KG SEX: FEMALE DAYS: ALL
PAGE 2 FATES; ALL
ANIMAL MO: 3060 PATHOLOGY ID. NO: 853060 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3041 PATHOLOGY ID, NO: 853061 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
ANIMAL NO: 30NGL
ANIMAL NO: 3063 PATHOLOGY ID. NO: 8S3063 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>RT. KIDNEY-PELVIS DILATED, KIDNEY- HYDRONEPHROSIS
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESGL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID; OCRESOL GROUP: 50 MG/KG SEX; FEMALE DAYS; ALL
.PAGE 3 ' FATES: ALL
ANIMAL NO: 3064. PATHOLOGY ID. NO; 853064 ' PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3065 PATHOLOGY ID. NO: 853065 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
ANIMAL NO: 3046 PATHOLOGY ID. NO: 853066 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3067 PATHOLOGY ID. NO: 853067 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ~~ DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>N6L
{Report Continued)
IV-2Q
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL • GROUP: 50 MG/KG SEX: FEMALE DAYS: ALL
PAGE 4 FATES: ALL
ANIMAL NO: 3063 PATHOLOGY ID. NO: 853068 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3069 PATHOLOGY ID. NO: 853049 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH! DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLQGY:
NGL
ANIMAL NO: 3070 PATHOLOGY ID. NO: 853070 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: . DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3071 PATHOLOGY ID. NO: 853071 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATHs DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOOY:
>NGL
(Report Continued)
IV-21
-------
PATHOLOGY ASSOCIATES, INC.
QRTHO-CRESOL
STUDY NO. 5221.0*
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & M'icro Findings
PROJECT ID: OCRESOL GROUP: 50 MG/KG SEX; FEMALE DAYS: ALL
PAGE 5 " FATES: ALL
ANIMAL NO: 3072 PATHOLOGY ID. NO: 853072 PATHOLGSIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST:. 92
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHQLOGY:
>NGL
ANIMAL NO: 3073 PATHOLOGY ID. NO: 853073 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: • DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
ANIMAL NO: 3074 PATHOLOGY ID. NO s 853074 PATHOLOGIST: DSC
ANIMAL FATEs SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TESTi 93
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY:
>NGL
ANIMAL MO: 3075 PATHOLOGY ID. MO: 853075 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: -• DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
I
>NGL ' I
(End o* Report)
IV-22
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESQL
STUDY MO. 5221.06
SPRAGUE-DAULEY RATS
Correlation o-f Gross &. Micro Findings
PROJECT ID: OCRESOL GROUP: 175MG/KG SEX:'HALE DAYS: ALL
PAGE 1 FATES: ALL
ANIMAL NO: 2957 PATHOLOGY ID. NO: 852957 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
-PROBABLE CAUSE OF DEATH: DAYS ON TEST: 9Z
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOQY;
>NGL
ANIMAL NO: 2958 PATHOLOGY ID. NO: 85295B PATHOLOGIST: DSC
ANIMAL FATEJ SCHEDULED SACRIFICE ;
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92-
.EFERENCE TO NECROPSY RECORDi RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NOs 2959 PATHOLOGY ID. NO: 852959 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ' DAYS ON TESTs 91
REFERENCE TO NECROPSY RECORD! RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NOi 2960 PATHOLOGY ID. NO: B529cSO ' PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST! 91
REFERENCE TO NECROPSY RECORD; RELATED HISTOPATHOLOGY:
>NGL
IV-23
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC
QRTHO-CRESOL
STUDY NO. 522!,06
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Firidings
PROJECT ID: OCRESOL GROUP: 175MG/KQ SEX: MALE DAYS: ALL
PAGE 2 " FATES: ALL
ANIMAL NO: 2961 PATHOLOGY ID, NO: 852961 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST; 91
REFERENCE TO NECROPSY RECORD: .RELATED HISTOPATHOLOGY:
>NGL
ANIMAL ND: 2962 PATHOLOGY ID. NO: 352962 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
4GL
ANIMAL NO: 2963 PATHOLOGY ID. NO: 852963 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST.- 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2964 PATHOLOGY ID. NO: 852964 PATHOLOGIST.- DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: . --' DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY!
>NGL
(Report Continued)
IV-24
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 5221.0*
SPRAGUE-DAWLEY RATS
Correlation o-f Oross & Micro Findings
PROJECT ID: OCRESOL CROUP: 175MG/KG SEX: MALE DAYS: ALL
PAGE 3 FATES! ALL
ANIMAL MO: 2965 PATHOLOGY ID. MO: 852?o5 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: - RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO! 2966 PATHOLOGY ID. NO I 352966 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHQLOGY:
ANIMAL NO: 2967 PATHOLOGY ID, NO: 8S2967 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH! DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2968 PATHOLOGY ID. NO: 852968 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH! - DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: P.ELATED HI STOPATHOLOGY:
>NGL
(Report Continued)
IV-25
-------
PATHOLOGY ASSOCIATES', INC
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP: 17SM6/KO SEX; MALE DAYS: ALL
PAGE 4 ' FATES: ALL
ANIMAL NO: 2969 PATHOLOGY ID. NO: 35296? PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2970 PATHOLOGY ID. NO: 852970 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATHJ DAYS ON TEST.- 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
ANIMAL NO: 2971 PATHOLOGY ID. NO; 852971 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>KIDNEY3-MOTTLED KIDNEY- NEPHRQPATHY, CHRONIC
ANIMAL NO: 2972 PATHOLOGY ID, NO: 852972 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: -' DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
(Report Continued)
IV-26
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221 ,Q6
SPRAQUE-OAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESQL . GROUP: 175MC/KG SEX: MALE DAYS: ALL
PAGE 5 FATES: ALL
ANIMAL NO: 2973 PATHOLOGY ID. NO: 352973 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; . DAYS ON TEST: 9:
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLQGY:
>PANCREAS-NODULE 4X3X1MM., TAN, MESENTERY-FAT NECROSIS
ATTACHED TO HESENTERIC FAT
ANIMAL NO: 2974 PATHOLOGY ID, NOs 852974 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: . DAYS ON TEST: 93
DEFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY;
/N6L
ANIMAL NO: 2975 PATHOLOGY ID. NO: 852975 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2976 PATHOLOGY ID, NO: 852976 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
IV-27
(End of Report)
-------
PATHOLOGY ASSOCIATES, INC.
ORTHQ-CRESOL
STUDY NO. 5221.06
SPRAGUG-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRE30L GROUP: 175MG/KG SEX:- FEMALE DAYS; ALL
PAGE I FATES: ALL
ANIMAL NO: 3039 PATHOLOGY ID. NO: 85303? PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY5
>NGL
ANIMAL NO; 3090 PATHOLOGY ID. NO: 853090 PATHOLOGIST: DSC'
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH! DAYS ON TEST: 92
'EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NOs 3091 PATHOLOGY ID. NO: 853091 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOQY:
>NGL
ANIMAL NO: 3092 PATHOLOGY ID. NO: 853092 -" PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS GN TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTCPATHCLOGY:
>NGL
IV-28
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAULEY RATS
Correlation o-f Sross & Micro Findings
PROJECT ID: OCRESOL GROUP; 175MG/KQ SEX: FEMALE DAYS; ALL
PAGE 2 ' FATES: ALL
ANIMAL NO: 30?3 PATHOLOGY 10. MO: 853093 PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: * . DAYS ON TEST; 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3094 PATHOLOGY ID. NO: 853094 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
ANIMAL NO: 3095 PATHOLOGY ID. NO: 853095 PATHOLOGIST: DSC
ANIMAL FATE.- SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY;
>NGL
ANIMAL NO: 3096 PATHOLOGY ID. NO: 853096 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: •'" DAYS ON TEST:- 91
REFERENCE TO NECROPSY RECORD: - RELATED HISTOPATHOLOGY:
>NGL
(Report Continued).
IV-29
-------
PATHOLOGY ASSOCIATE1!
ORTHO-CRES
STUDY NO. 52;
SPRAGUE-DAULE'i
Correlation o-F Gross & Micro Findings
PROJECT ID: OCRESOL
PAGE 3
GROUP! 175MG/KG
FATES: ALL
SEX: FEMALE
DAYS: ALL
ANIMAL NO: 3097 PATHOLOGY ID. NO: 853097
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH:
REFERENCE TO NECROPSY RECORD:
>KIDNEYS-BILATERAL PELVIS DILATION.
PATHOLOGIST: DS
DAYS ON TEST: 9
RELATED HISTOPATHOLQGY:
KIDNEY- HYDRCNEPHROSIS
ANIMAL NO: 3098 PATHOLOGY ID. NO: 853098
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH:
PATHOLOGIST: DS
DAYS ON TEST: 9
REFERENCE TO NECROPSY RECORDi
>NGL
RELATED HISTOPATHOLOGYs
ANIMAL NO: 3099 PATHOLOGY ID. NO: 853099
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH:
PATHOLOGIST: DS
DAYS ON TEST: 9
REFERENCE TO NECROPSY RECORD:
>NGL
RELATED HISTOPATHOLOGY:
ANIMAL NO:- 3100 PATHOLOGY ID, NO•, 8531 GO
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH:
PATHOLOGIST: DS<
DAYS ON TEST: 9
REFERENCE TO NECROPSY RECORD:
>NGL
RELATED HISTOPATHOLOGY:
(Report Continued)
IV-30
-------
PA i riU-Luur ASSOCIATES, INC.
ORTHQ-CRESOL
STUDY NO. 5221 .06
SPRAGUE-DAWLEY RATS
Correlation of Gross & Micro Findings
PROJECT ID; OCRESCL GROUP; 175MG/KG SEX: FEMALE DAYS; ALL
PAGE 4 - FATES: ALL
ANIMAL NO: 3101 PATHOLOGY ID. NO: 853101 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
)NGL
ANIMAL NO: 3102 PATHOLOGY ID, NO: 853102 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TESTs 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHQLOGY:
SNGL
ANIMAL NO: 3103 PATHOLOGY ID. NO: 853103 PATHOLOGIST! DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: • DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3104 PATHOLOGY ID. NO: 853104 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH! ; DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NSL
(Report Continued")
IV-31
-------
PATHOLOGY ASSOCIATES, INC.
QRTHO-CRESOL
STUDY NO. 5221 ,06
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP: I75MG/KG SEX.- FEMALE DAYS: ALL
PAGE 5 • FATES: ALL
ANIMAL NO: 3105 PATHOLOGY ID, NO: 853105 PATHOLOGIST! DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST; 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3106 PATHOLOGY ID. MO: 853106 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
MGL
ANIMAL NO: 3107 PATHOLOGY ID. NO: 853107 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3108 PATHOLOGY ID. NO: 353108 PATHOLOGIST; DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: ; DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD! RELATED HISTOPATHOLOGY:
>NGL
(End of Report)
1V-32
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 5221,06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: QCRESQL GROUP; 60QMG/K6 SEX:. MALE DAYS: ALL
PAGE 1 FATES: ALL
ANIMAL NO; 2934 PATHOLOGY ID. NO: 852934 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST] 17
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>LIYER-MOTTLED AND DARK LIVER- CONGESTION
>INTESTINES-DARK AUTOLYSIS; MILD
>LUNG-LEFT LOBE DARK RED LUNG- CONGESTION; NO INFLAMMATION
ASSOCIATED WITH BACTERIA
>TRACHEA-HAS OIL IN IT NO COROLLARY CHANCE DETECTED
ALL TISSUES MILD TO MODERATE
AUTOLYSIS
ANIMAL NO: 2990 PATHOLOGY ID. NO; 852990 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOOY:
>NGL
ANIMAL NO: 2991 PATHOLOGY ID, NO: 852991 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY;
>NGL
IV-33
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC
QRTHO-CRESQL
STUDY NO. 5221.Oi
SPRAGUE-DAULEY RATS
Correlation a-f Gross & Micro Findings
PROJECT ID: QCRESOL . GROUP: 4QQMG/KG SEX: MALE DAYS: ALL
PAGE 2 ' FATES: ALL
ANIMAL NO: 2992 PATHOLOGY ID. NO: 852992 PATHOLOGIST: DSC
ANIHAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 2
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHQLGGY:
>LUNGS-MDTTLED LUNG- CONGESTION
>LIVER-DARK'RED LIVER- CONGESTION
ANIMAL NO: 2993 PATHOLOGY ID. NOs 852993 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 9
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
XTISSUE PARTIALLY AUTOLYZED; NVL
> - TISSUES MILDLY AUTOLYTIC, MAMMARY
GLAND ASSOCIATED WITH MUSCLE
SPECIMEN
ANIMAL NO: 2994 PATHOLOGY ID. NO: 852994 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: . DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHQLQGY.
>NGL
(Report Continued)
IV-34
-------
PATHOLOGY ASSOCIATES, INC
CRTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-F Gross &. Micro Findings
PROJECT ID: OCRESOL GROUP: 400MG/KO SEX: MALE DAYS: ALL
PABE 3 ' FATES: ALL
ANIMAL NO; 2995 PATHOLOGY ID. NO: 352995 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH; " DAYS ON TEST: 35
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>LUNGS-MOTTLED RED LUNG- CONGESTION; PRESENCE OF OIL
DROPLET IN LUNGS SUGGESTS
INHALATION. LYMPHQCYTIC CUFFS IN
LUNG INCLUDED PLASMA CELLS.
ANIMAL NO; 2996 PATHOLOGY ID. NO; 852996 PATHOLOGIST: DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH-, DAYS ON TEST: 91
.EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2997 PATHOLOGY ID. NO: 852997 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 18
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>OIL IN TRACHEA MO COROLLARY CHANGE DETECTED; NO
EVIDENCE OF OIL IN LUNG
(Report Continued)
IV-35
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 522i.06
SPRAGUE-DAULEY RATS
Correlation o-f Gross &. Micro Findings
PROJECT ID: OCRE30L GROUP: dCOMG/KG SEX: MALE DAYS: ALL
PAGE 4 " FATES: ALL
ANIMAL NO: 2998 • PATHOLOGY ID. NO: 852998 PATHOLOGIST; DSC
ANIMAL FATE; SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 2999 PATHOLOGY ID. MO 5 852999 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY;
JGL
ANIMAL NO: 3000 PATHOLOGY ID. NO: 353000 PATHOLOGIST! DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST; 64
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY;
>LUNGS-RED MOTTLED, INFLATED LUNG- CONGESTION
>NASAL CAVITY-OIL NO COROLLARY CHANGE DETECTED
>ESOPHAGUS & STOMACH-SMALL AMOUNT OF NO COROLLARY CHANGE DETECTED
OIL
(Report Continued)
IV-36
-------
I HUL.UU'» rti>isUl_i A l"tS , INC.
ORTHO-CRESOL
STUDY NO. 5£Z:,06
SPRAGUE-DAWLEY RATS
Correlation of Gross & Micro Findings
PROJECT ID; OCRESOL GROUP: 60QMG/KG SEX: MALE DAYS: ALL
PAGE 5 FATES: ALL
ANIMAL NO: 3001 PATHOLOGY ID. MO: 853001 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST; 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
> INFLAHMATIONCGRANULQMATOUS) IS IN
C.T. ASSOCIATED WITH THYROID AND
CONTAINS FOREIGN-BODY GIANT CELLS
ANIMAL NO: 3002 PATHOLOGY ID. NO: 853002 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
^QSABLE CAUSE OF DEATH: DAYS ON TEST: 93
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3003 PATHOLOGY ID. NO: 853003 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NCL
(Report Continued)
IV-37
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: QCRESQL GROUP: 600MG/K6 SEX: MALE DAYS: ALL
PAGE 6 ' FATES: ALL
ANIMAL MO: 3004 PATHOLOGY ID. MO: 353004 PATHOLOGIST: OSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH; . DAYS ON TEST: 2
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY!
>NGL
> • TISSUES-MILD AUTQLYSIS
ANIMAL NO: 3005 PATHOLOGY ID. NO: 653005' PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NOL
ANIMAL NO: 3006 PATHOLOGY ID. NO: 853006 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: - . DAYS ON TEST: 46
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHOLOGY:
>MOUTH & NOSE-OIL AROUND THEM NO COROLLARY CHANGE DETECTED
>LUNGS-MOTTLED RED LUNG- CONGESTION
>SPLEEN- ONE HALF DISCOLORED, BLACK AUTOLYSIS-MODERATE
> ALL TISSUES MILD TO MODERATE
AUTOLYSIS
(Report'Con tinued)
IV-38
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESDL
STUOY NO. 5221,06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross. & Micro Findings
PROJECT ID; OCR.ESOL GROUP; 6QOMG/K3 SEX: MALE DAYS; ALL
PAGE 7 FATES: ALL
ANIMAL NO: 3007 PATHOLOGY ID. NO: 853007 PATHOLOGIST; DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: " DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLQGY:
>KIDNEYS-SLIGHTLY MOTTLED NO COROLLARY CHANGE DETECTED
ANIMAL NO: 3003 PATHOLOGY ID. NO: 853008 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TESTs 9
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
NGL
ANIMAL NO: 3009 PATHOLOGY ID. NO: 853009 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 92
REFERENCE TO NECROPSY RECORDS RELATED HISTOPATHOLOGYs
>NGL
-------
PATHOLOGY ASSOCIATES, INC.
OR7HO-CRESOL
STUDY NO, 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP; 60QMG/KG SEX: FEMALE DAYS: ALL
PACE 1 • FATES: ALL
ANIMAL NO: 3112 PATHOLOGY ID. NO: 353112 ' PATHOLOGIST: DSC'
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS DM TEST: 16'
REFERENCE TO NECROPSY RECORD: . RELATED HISTOPATHOLOQY:
>LUNGS DARK RED, FIRM, AND FAILED TO LUNG- CONGESTION, LUNG- EDEMA
COLLAPSE
>0!L IN TRACHEA NO COROLLARY CHANGE DETECTED. OIL
DROPLET IN LUNGS SUGGESTS
ASPIRATION,
ANIMAL NO: 3113 PATHOLOGY ID. NO: 853113 PATHOLOGIST: DSC
ANIMAL FATE; FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 35
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>MESENTERY-NECROSIS FAT, 5X5MM NECROTIC FAT NOTED AT TRIM IS
BROWN; DETECTED AT TRIM AUTOLYTIC PANCREATIC LN, MESENTERIC
FAT, AND PANCREAS UJITH A SMALL
AMOUNT OF NECROTIC FAT SURROUNDING.
> ALL TISSUES ARE MILDLY TO
MODERATELY AUTOLYTIC.
ANIMAL NO: 3121 PATHOLOGY ID. NOs 853121 " PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 0
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>LUNGS-MOTTLED-ALL LOBES LUNG- EDEMA
yLIVER-DARK MILD AUTOLYSIS
>KIDNEYS-DARK MILD AUTOLYSIS
IV-40
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO, 5221.06
SPRAGUE-DAUILEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID; OCRESOL - GROUP: 400MC/KG SEX: FEMALE DAYS; ALL
PAGE 2 FATES: ALL
ANIMAL NO: 3121 PATHOLOGY ID. NO: 853121 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 0
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY: :
> ALL TISSUES MILDLY AUTOLYTIC. ALSO
EVIDENCE OF ARTIFACTS DUE TC
FREEZING, PRESENCE OF OIL IN LUNG
SUGGESTS INHALATION.
ANIMAL NO: 3122 . PATHOLOGY ID. NOs 853122 PATHOLOGIST: OSC
ANIMAL FATE: FOUND DEAD
CROBABLE CAUSE OF DEATH: DAYS ON TEST: 18
REFERENCE TO NECROPSY RECORD: . RELATED HISTOPATHOLOGY!
>LUNGS-RED, MOTTLED. ' LUNG- CONGESTION. NO EVIDENCE OF
OIL IN LUNG.
ANIMAL NO; 3123 • PATHOLOGY ID. NO: 853123 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: IS
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>LUNGS-RED, MOTTLED LUNG- CONGESTION
>MANDIBULAR LYMPH NODE-RED, RIGHT MANDIBULAR LYMPH NODE- CONGESTION
SIDE
-------
PATHOLOGY ASSOCIATES, JNC
ORTHO-CRESOL
STUDY NO. 5221.06
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL QROUP: ^QOMG/KG SEX: FEMALE DAYS: ALL
PAGE 3 ' FATES: ALL
ANIMAL NO: 3124 PATHOLOGY ID. MQ; 853124 ' PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: . DAYS ON TEST: 33
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
> ALL TISSUES MILD TO MODERATE
AUTOLYSIS
ANIMAL NO: 3125 PATHOLOGY ID. NO: 8S3125 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: ' DAYS ON TEST: 35
>EFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOQY:
>NQL
> TISSUES MILDLY TO MODERATELY
AUTOLYTIC.
ANIMAL NO: 3126 PATHOLOGY ID. NO: 853126 PATHOLOGIST: DSC
ANIMAL FATES FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 32
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>OIL FLOWED FROM TRACHEA NO COROLLARY CHANGE DETECTED
>LUNGS-RED AND MOTTLED ' LUNG- CONGESTION, NO REACTION
(INFLAMMATION, ETC.) ASSOCIATED
WITH BACTERIA IN L-Jwl5
>LIMER-DARK RED LIUER- CONGESTION
^INTESTINES STARTED TO FORM OAS AUTOLYTIC CHANGE, MILD
(Report Continued)
IV -42
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESOL
STUDY MO. 5221,06
SPRAGUE-DAULEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRESOL GROUP: 600H6/KG SEX; FEMALE DAYS: ALL
PAGE 4 FATES: ALL
ANIMAL NO; 3126 PATHOLOGY ID. NO: 853126 PATHOLOGIST; DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 3;
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>RED STAIN-NOSE INTESTINE-DISTENDED WITH GAS MILD AUTOLYSIS
>STOMACH-DISTENDED WITH GAS . MILD AUTOLYSIS
ANIMAL NO: 3128 PATHOLOGY ID. NO: 853128 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: B9
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>JEJUNUM AND ILEUM ARE RED MILD AUTOLYSIS
>HEART SLIGHTLY ENLARGED NO COROLLARY CHANGE DETECTED
>LUNGS MOTTLED LUNG- CONGESTION. NO EVIDENCE OF
OIL IN LUNG
(Report Continued)
IV-43
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRESQL
STUDY NO. 5221 ,06
SPRABUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID; OCRESOL GROUP; 600HG/KG -SEX: FEMALE DAYS; ALL
PAGE 5 " FATES: ALL
ANIMAL NO': 3129 PATHOLOGY ID. NO: 853129 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHOLOGY:
>LUNGS-MOTTLED NO EVIDENCE OF OIL IN LUNG. LUNG-
CONGESTION
>LEFT KIDNEY-ENLARGED; PALE-PELVIS; KIDNEY- HYDRONEPHROSIS
MILDLY DILATED.
ANIMAL NO: 3130 PATHOLOGY ID, NO: 853130 . . PATHOLOGIST! DSC
ANIMAL FATE: SCHEDULED SACRIFICE
30BABLE CAUSE OF DEATH; DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>NGL
ANIMAL NO: 3131 PATHOLOGY ID. NO: 853131 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 17
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>ALL TISSUES APPEAR DARK ALL TISSUES MILD TO MODERATE
AUTQLYSIS
>INTESTINE SOFT AUTOLYSIS
>LIUER MOTTLED LIVER- CONGESTION
>LUNGS MOTTLED LUNG- CONGESTION
(Report Continued)
IV-44
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY NO. 5221 .06
SPRAGUE-DAUJLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID; OCRE30L
PAGE 6
GROUP: 600MG/KG
FATES: ALL
SEX: FEMALE
DAYS: ALL
ANIMAL MO: 3132
ANIMAL FATE; FOUND DEAD
PROBABLE CAUSE OF DEATH:
PATHOLOGY ID. MO: 853132
REFERENCE TO NECROPSY RECORD:
>0!L AROUND NOSE
>RED MOTTLED LUNGS
PATHOLOGIST: DSC
DAYS ON TEST: 14
RELATED HISTOPATHOLOGY:
MO COROLLARY CHANGE DETECTED
LUNG- CONGESTION
ANIMAL NO: 3133
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH:
PATHOLOGY ID, NO: 853133
IFERENCE TO NECROPSY RECORD:
>RED MOTTLING ON ALL LOBES OF THE
LUNGS
PATHOLOGIST: DSC
DAYS ON TEST: 12
RELATED HISTOPATHOLOGY:
LUNS- CONGESTION. NO EVIDENCE OF
OIL IN LUNG.
ANIMAL NO: 3134
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH:
PATHOLOGY ID. NO: 853134
REFERENCE TO NECROPSY RECORD:
>TISSUES APPEAR DARK
>NO OIL IN TRACHEA
>INTESTINES AUTQLYZED
PATHOLOGIST: DSC
DAYS ON TEST: 17
RELATED HISTOPATHOLOGY:
MODERATE AUTOLYSIS OF TISSUES
NO COROLLARY CHANGE DETECTED
MODERATE AUTOLYSIS OF TISSUES
(Report Continued)
IV-45
-------
rrtiHQi_UGY AobliCiATCS, INC,
ORTHO-CRE30L
STUDY NO. 5221.06
SPRAGUE-DAULEY RATS
Correlation 0-6 Gross & Micro Findings
PROJECT ID: QCRESOL GROUP: 6QOMG/KG SEX; FEMALE DAYS: ALL
PAGE 7 • FATES: ALL
ANIMAL NO: 3135 PATHOLOGY ID. NO: 853135 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHOLQGYs
>RT. KIDNEY-PELVIS DILATED. NO COROLLARY CHANGE DETECTED
ANIMAL NO: 3136 PATHOLOGY ID. NO: 853136 PATHOLOGIST: DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH; DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTDPATHOLOGY:
NGL
ANIMAL NO: 3137 PATHOLOGY ID. NO: 853137 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 9
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY:
>ALL TISSUE PARTIALLY AUTOLYZED. ALL TISSUE MILD TO MODERATE
AUTOLYSIS
ANIMAL NO: 3138 PATHOLOGY ID. NO: 853138 PATHOLOGIST; DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: ' ' DAYS ON TEST: 8
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGY5
>LUNG3 MOTTLED RED LUNG- CONGESTION
^EVIDENCE OF OIL IN THE STOMACH NO COROLLARY CHANGE DETECTED
IV-46
(Report Continued)
-------
PATHOLOGY ASSOCIATES, INC.
ORTHO-CRESOL
STUDY MO. 5221.06
SPRAGUE-DAWLEY RATS
Correlation o-f Gross & Micro Findings
PROJECT ID: OCRE30L GROUP; 6QGMG/KG SEX: FEMALE DAYS: ALL
PAGE 3 ' FATES: ALL
ANIMAL NO: 3139 PATHOLOGY ID. NO: B5313? PATHOLOGIST! DSC
ANIMAL FATE: SCHEDULED SACRIFICE
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 91
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHOLQGY:
>NGL
ANIMAL NO: 3140 PATHOLOGY ID. NO: 853140 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 18
REFERENCE TO NECROPSY RECORD: RELATED HISTQPATHOLQGY:
3ED MOTTLED LUNGS LUNG- CONGESTION
ANIMAL NOi 3141 PATHOLOGY ID. NO; 353141 PATHOLOGIST: DSC
ANIMAL FATE: FOUND DEAD -
PROBABLE CAUSE OF DEATH: DAYS ON TEST: 35
REFERENCE TO NECROPSY RECORD: RELATED HISTOPATHOLOGYs
>NGL
> ALL TISSUES MILD TO MODERATE
AUTOLYSIS.
(End of Report)
IV-47
-------
2888
2889
2915
2921
2923
2947
2948
2949
2950
GROSS AND MICROSCOPIC FINDINGS
45 DAY SACRIFICE
Animal No. DflS£_fijL
2881 Op. 1
Qp. 1
Gp. 1
6p. 2
Gp. 2
Op. 2
Gp. 3
Qp. 3
Gp.3
Op. 3
MALES
Gross Observation
Kidney-slight mottling
tan/red
Kidneys-both pale and
mottled
Microscopic QbseryjtiQD
No corresponding lesion
Nephropathy, chronic, minimal
RL and Lt Kidneys- pelvis No corresponding lesion
dilated
Kidney-slightly mottled
red/tan
Liver-round, (5-7mm)
dark tan mess, accessory
lobe-upon incision filled
with clotted blood
Nephropathy, chronic, minimal
Infarct, accessory lobe, severe
Lumbar LN-enlarged Hemorrhage, acute, mild
Kidneys-mottled red/tan No corresponding lesion
Kidneys-pale, brown
Nephropathy, chronic, minimal
Prostate-rt. lobe-enlarged Normal secretion dilates the gland.
Dilation, glands, mild
Kidney-darken flat foci No corresponding lesion
(Less than or equal to ,3mm)
(barely perceivable) on
cortical surface. Both
kidneys pale.
Kidneys-pale
Kidneys-both pale and
mottled
Kidneys-botn pale and
mottled, red and tan
No corresponding lesion
Nephropathy, chronic, minimal
No corresponding lesion
IV-48
-------
GROSS AND MICROSCOPIC FINDINGS
. 45 DAY SACRIFICE
. MALES (cont.)
Animal Ife. Dose 6p. Gross Observation Microscopic Observation
2951 Op. 3 Mandibular LN-slightly
enlarged
Kidneys-pale
2954 6p, 3 Kidneys-both pale
2955 Gp. 3 Mandibular LN-enlarged
(8x4x3 mm)
P restate-Rt. lobe-enlarged
Kidneys-pale
2956 Qp. 3 Rt. & Lt. kidney-pelvis
dilated
2982 Gp. 4 Kidney-both pale
2985 Op. 4 Kidneys-pale
Lympnoid hyper plesia, moderate
No cor responding lesion
No corresponding lesion
Lymphoid hyperplasia, moderate
Dilation, gland, mild
Nephropathy, chronic, minimal
No cor responding lesion
Nephropathy, chronic, minimal
No corresponding lesion
IV-49
-------
GROSS AND MICROSCOPIC FINDINGS
45 DAY SACRIFICE
FEMALES
Animal No. DoseGiL Gross Observation Hicrosmoic Observation
301?
3118
Gp.
3020
3046
3052
3079
3082
3083
3085
3087
3088
Op. 1
Op. 2
3p. 2
Op. 3
Sp.3
Gp. 3
Op. 3
Op. 3
Op. 3
Gp. 4
Kidneys-both pelvis
dilated
Rt & Lt. kidneys-pelvis
dilated
Liver-hernia (3x3x2mm)
median lobe
Mandibular Nodes-enlarged
Kidneys-both pale
Mandibular LN-enlarged
(10x5x3mm)
Mandibular LN-enlarged
Kidneys-si ightly mottled
Kidneys-slightly mottled
Liver-Rt. lobe rounded
edges (2.0x1.Ox 1.0cm)
Lt Kidney-moderate
enlargement of renal pelvis
Rt kidney-minimal
enlargement of renal pelvis
Hydronephrosis, minimal
One pelvis dilated. Other pelvis within
normal range.
Hydronephrosis, mild
Lesion not identified in wet tissue.
Lymphoid hyperplasia, mild
No corresponding lesion
Lymphoid hyperplasia, moderate
Lymphoid hyperplasia, mild
No corresponding lesion
No corresponding lesion
No corresponding lesion
Hydronephrosis, multifocal, minimal
Hydronephrosis, multifocal, minimal
IV-50
-------
V. QUALITY ASSURANCE REPORT
-------
-------
THIS PAGE REVISED
ft /i /) il II study"°-
(MM) 6 . UtUMlfW }
'
1- 16- it,
QUALITY ASSURANCE STATEMENT
This hlstopathology project has been conducted In compliance with Good
laboratory Practice regulations promulgated oy the U. 5. Food and Drug
Administration and the U. 5. Environmental Protection Agency. Pathology
Associates, incorporated has a functioning and responsive quality
assurance unit which has conducted appropriate inspections and reported
all findings to management The following is a record of those Inspections
and reports:
Date Findings Reported
Date of to Management
inspection* Phase Inspected and Study Pathologist
**01-07-86 Tissue Trimming 01-09-86
**Q 1-09-86 Processing 01-14-86
**01-09-86 Embedding 01-H-86
* 02-19-86 Microtomy 02-19-86
* 02-19-86 Staining 02-19-86
* 02-19-86 Coverslipping 02-19-86
* 02-10-86 Labeling 02-10-86
**Q4-14-86 Individual Animal Data 05-01-86
**04-15-86 Data Entry 05-01-86
**04-15-86 Computer Validrtion 05-01-86
**04-23- 86 Dran Pathology Report 05-01 -86
**05-3Q-86 Final Pathology Report 05-30-86
**Q8-12-86 Revised Final Pathology Report 08-12-86
* General monthly phase inspection
** Inspection specific for Study Number
fln accordance with the PA1 Quality Assurance Division's Standard Operating
Procedures, phase inspections are routinely conducted on a random basis at a
minimum of monthly. Dates of inspection are reported for each study
according to the most recent phase inspection conducted during that period.
August 12, 1986
: Director, Qualit^y4surance Unit Date
"Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats."
Study Number 5221.06
V-l
-------
-------
APPENDIX 1
REPORTS CODE TABLE
v-L
-------
-------
PATHOLOGY ASSOCIATES, INC
ORTHO-CRE3QL
STUDY NO. 5221.06
SPRAGUE-DAWLEY RATS
Reports Code Table
N Tissues within normal histoiogical limits
A Autolxsis precluding a'dequate evaluation
U Tissues unauai1able/unsuitab!e for evaluation
S Tissues not applicable to animal
* Tissues not examined/not required bx protocol
I mini mal
2 mild
3 moderate
4 severe
) -focal
] diffuse
> mu 1 t i focal
P Present
B Neoplasm, Benign
M Neoplasm, Malignant without Metastasis
C Neoplasm, Malignant with Metastasis
X Metastat ic Si te . <-O
(End of Repor t)
-------
-------
APPENDIX 2
ABBREVIATION LIST
-------
-------
ABBREVIATION LIST
INFLAMMATION
PERI VASCULAR
MUSCLE
EXTRAMEDULLARY HEMATOPOIES1S
INTERSTITIAL
LYMPH NODE
INGUINAL
EPITHELIAL
LYMPHOCYTIC
HARDERIAN GLAND
INFLAM
PERIV
M.
EMH
INTERSTIT
LN
ING.
EPITH.
LYMPHOCY.
HARD. GL.
v-5
-------
-------
APPENDIX G
PROTOCOL, AMENDMENTS AND DEVIATIONS
MICROBIOLOGICAL
ASSOCIATES INC.
-------
-------
ORIGINAL
Experiment Number 5221.06
Received • by RA/QA
SUBCHRONIC TOXICITY OF ORTHO-CRESOL IN
SPRAGUE DAWUEY RATS
I. PURPOSE
The purpose of this study is to determine the toxic effects of
o-cresol when administered by gavage for 13 weeks to Sprague Dawley
rats.
II. SPONSOR AND TESTING FACIIJTY
A. Sponsor Name: Research Triangle Institute (RTI)
B. Sponsor Authorization Date: 12 July 1985
C. Protocol Approval_ Date' (See last page)
D. Testing Facility: Microbiological Associates Inc.,
5221 River Road
Eethesda, Maryland 20816
E. Princigal_Ir^/estiqator (Study=Dirict.Qr]_: Louis T. Mulligan, Ph.D.
F. Toxicoloqist: Earry S. Levine, D.Sc., D.A.B.T.
III. TEST SCHECULE
A, Sctiedxiled Initiation Date*. 3 September 1985
B, Proposed Termination Date: 3 December 1985
G - 2
1
-------
-------
Experiment Number 5221.06
IV. TEST ARTICLE
A. Name: o-cresol
B. Source and Manufacturer
Source: Eastman Kodak Company
Rochester, NY 14650
Manufacturer: To be supplied
Lot No.: B-12-B
Batch No.: None
Purity: 99% +
In-house Chemical No.: 23
C. .Safety Precaut ions
1. Personnel Protection
Eye: Safety goggles
Gloves: Two pairs of gloves should be worn when
handling the neat chemical; one pair of
gloves should be worn when' handling dose
preparations,
Clothing: Protective laboratory clothing will be
worn when handling dose preparations or
neat chemical,
Ventilation: Handling of open dosage containers
or chemical should be conducted in a
properly vented hood.
Respirator: A respirator fitted with an organic
vapor (or organic vapor/acid vapor)
cartridge equipped with a particulate
filter will be used at all times when
working with open containers and when
working in roams with animals dosed
with this chemical.
G - 3
2
-------
Experiment Number 5221.06
Spillsand Leakage
Persons not wearing the appropriate protective
equipment and clothing should be restricted from
areas of spills or leaks until cleanup has teen
coupleted.
If c-cresol or solutions of it are spilled the following
steps should be taken:
a. Ventilate area of spill. Eliminate all heat
and ignition sources.
b. Use vermiculite, sodium bicarbonate, sand, or
paper towels to absorb the oil.
c. Wash area with detergent and water or Mico-
klene and water. Rinse well with water.
d. Dispose of all material in the cleanup as
hazardous waste,
Waste and Disposal Procedures
Securely package and label, in double bags, all
solid waste material and dispose of by
incineration or by burial at a secured landfill.
Dispose of liquid waste in liquid hazardous waste
drums.
Preparation., of Doses
Doses will be prepared in the Carcinogen Handling
Room, 3rd floor, 5221 River Road, Eethesda, MD. 20853.
G - 4
3
-------
Experiment Number 5221.06
5, Analysis of .Solutions
The stability of the test solution will be determined
after storage for the same period and under the same
condition to be used in the study.
The accuracy of formulation will be checked by analysis
of samples taken from solutions prepared for administration
during weeks 1, 2, 4, 8 and 13 of treatment.
V. TEST SYSTEMS'
A. Animals
1. Strain/Species: Sprague Dawley Eats
2. Number/Sex: 130 males/130 females
3. Age; 5-6 weeks old at start of dosing
4. Supplier: Charles Mver Breeding Laboratories.
5. Justification of Test Animal: The test animal {Sprague
Dawley Rats) was specified by the sponsor and is a routine
laboratory animal utilized in small rodent subchronic toxicology
studies.
VI. HOUSING
The animals will be individually housed in polycarbonate shoe boxes
marked with a test article code and held on stainless steel racks
equipped with an automatic watering system. Heat treated hardwood
chips will be used for cage bedding. Racks will be periodically
repositicned within the room to minimize any effect of variation in
light intensity, temperature, etc.
VII. ANIMAL ENVIRONMENT
A. Temperature: 72° + 3°F
B. Humidity: 50 ± 15%
C. Light Cycle: 12 hour cycle
D. Water: _-Washington Suburban Sanitary Commission Potomac
Plant; untreated; ad libitum.
E. Feed: Purina standard lab chow.
G - 5
4
-------
VIII.
Experiment Number 5221.06
F. Cage Change ^ Schedule: Cages will be changed every other weak.
G. Feeder Change Schedule: Once weekly.
H. Rack Changes; Every other week.
I. Air Change: At least 12-15 per hour.
,J. Bedding Changes: Twice weekly.
K. Room Number: Room #371
L. It is not expected that there are contaminants in the feed or
water which would have any influence on the study.
A. Animals will be maintained in quarantine for 12-15 days. The
housing, cleaning, feeding and watering procedures will be the
same as described above for the test period.
B. Animals will be observed twice daily for signs of illness or
death and all unusual observations will be reported to- the Princiral
Investigator or Director of Veterinary l-ledicine.
C. Animals will be examined during quarantine and approved for use
by the Director of Veterinary Medicine prior to being placed on
test. Health Status Evaluation form RA/QA 11 will be completed
by the Study Director and Director of Veterinary Medicine.
IX. RANDOMIZATION x ANIMAL NUMBERING >_ STATISTICAL ANALYSIS
A. Randomization: During the quarantine period, the animals will be
randomized as follows: Starting with one sex of the species to be
randomized, each animal will be weighed, placed into individually
numbered cages and separated into one of a number of weight range
groups which are based en successive intervals of 5 grams. The
weight of each is recorded on paper. After all animals^have been
placed into their appropriate weight range groups, 120 of the animals
with weights closest to the median weight will be randomized.
Outliers will be used for health check evaluation and baseline
evaluations or killed.
After the appropriate number of animals per sex have been selected,
a random number table will be computer generated for each of the
sexes. After aniirals have been randomized to cages, a separate
set of random numbers will be generated and used to allocate cages
to a dose group.
G - 6
5
-------
Experiment Number 5221.06
B. Numbering: Animals will be uniquely consecutively numbered using
tee clips.
C. Statistics: The data will be examined using analysis of variance
techniques followed by a multiple conparison procedure for detecting
differences between pairs of means. Some pathology and clinical
data may require nonparametric techniques to aid in interpretation.
X. EXPERMEOTAL METHODS
A. Dosing
1. Route: Gavage (specified by sponsor)
2. Vehicle: Corn Oil
3. Frequency; Daily, approximately the same time each day,
7 days a week, for a total period of 13 weeks.
4. Dosage Volume: Five (5) ml/kg calculated on animal's most recent
bcdy weight.
5. Controls: Receive vehicle alone at the same dosage volume
as treated animals.
6. Mixing Frequency: Dosing solutions will be mixed on a weekly
basis and kept refrigerated at 4°C.
G - 7
6
-------
Experiment Nujrfcer 5221.06
B. Treatment _GrouPS
Animals will be randomly assigned to groups with the following
design:
Number of Animals
Dose Level
Group Treatment fang/kg/day) Male Female
1 Negative control — 30 30
2 c-cresol TBD "30 30
3 o-cresol TBD 30 30
4 o-cresol TBD 30 '30
5 Baseline clinical • 10 10
pathology
The ten male and ten female animals in group §5 will be sacrificed
prior to study initiation for collection of baseline data on
hematology and serum chemistry.
Ten male and ten female animals (selected prior to initiation of
the study) from each remaining group will be sacrificed at 45-days
post-treatment for clinical pathology and collection of tissues
for possbile later evaluation. The following organs will be
weighed: heart, liver, spleen, brain, kidneys (individually), gonads
(individually), adrenals and thyroid/parathyroid.
C. Clinical Observations
1. Animals will be observed twice daily (once in the morning and
once in afternoon) seven days per week for moribund!ty/mortality.
Moribund animals unlikely to survive until the next observation
will be sacrificed and necropsied immediately.
2. Each animal will be examined weekly for clinical signs of
toxicity.
3. Signs of toxicity noted at other times will be recorded on
room schedules and transferred to the observation sheet if they
persist.
4. Animal Weights - Individual animal weights for test and control
groups will be recorded at initiation (day 1) and weekly
thereafter.
G - 8
7
-------
Experiment Number 5221.06
5. Individual feed, consumptions will be derived by calculating
the difference in weight of each feed jar plus contents at
the beginning and end of the feeding interval and dividing by
the number of days involved. An estimate of the mg of test
material consumed/body weight/day will then be calculated,
D. OphthaImoscopv
Funduscopic (indirect opthalmoscopy) and bicmicroscopic (slitlarnp)
examinations will be performed pretreatment and at termination on
all animals designated to be terminated at 13-weeks.
E. Clinical Pathology
1. The following hematolcgy (all animals fasted overnight) will
be performed on the 20 animals designated for baseline values
(day 1), on 10 males and 10 females/group designated to be
sacrificed at 45 days and on 10 males and 10 females/group
designated to be sacrificed at termination of the study:
Hemoglobin
Hematccrit
Erythrocyte count
Total and differential leukocyte count
Flatlet count
Reticulccyte count
2. The following clinical chemistry will be determined on serum
samples per the hematology schedule:
Sodium
Chloride
Potassium
Phosphorus
Blood creatinine
co2
SGPT
SCOT:
Glucose
BUN
Direct and total bilirubin
SAP
Total cholesterol
Albumin
Globulin
Total protein
G - 9
a
-------
Experiment Number 5221.06
3. Urinalysis will be determined on days 45 and 90- as outlined
for clinical chemistry. The following parameters will be
measured:
Specific gravity
pH
Protein
Glucose
Ketones
Bilirubin
Urobilinogen
Microscopic examination
F, Necropsy and Histopathlogy:
1. A complete, detailed necropsy will be performed en all animals.
2. Animals that die or are sacrificed prior to the scheduled
sacrifice will be necropsied as soon as possible after death.
Animals that can not be necropsied immediately will be stored
in a refrigerator until necropsy but no longer than 24 hours.
3 . From all animals on study, except those designated for baseline
clinical chemistry the following tissues will be collected
and preserved in buffered formalin.
All gross lesions
Brain (3 levels)
Eye
Pituitary
Salivary gland
Heart
Thymus
Thyroid (with parathyroid)
Lungs (with mainstem bronchi)
Trachea
Esophagus
Stomach
Small and large intestine
Adrenals
Pancreas
Liver
Kidneys
Urinary bladder
Testes
Prostate
Ovaries
Corpus and cervix uteri
Spleen
Bone (with marrow)
Skeletal muscle .
Lymph node
Spinal cord
Mammary gland
Aorta
Sciatic nerve
G - 10
9
-------
Experiment Number 5221.06
4. Histcpathoiogical evaluation will be performed on all abnormal
tissues and lesions of all animals "on study. All listed
tissues will be saved from all rats at the 45-day sacrifice
for possible future evaluation. All the above listed tissues
will be evaluated on all animals sacrificed because of a moribund
condition, those that die on test, and all control and high-
dose animals sacrificed at the 13 week termination.
Histopathology in the mid and low dose groups will only be
required for gross lesions and apparent target organs. Target
organs will be determined from previous studies, clinical
data, and the histopathology in the high-dose level group.
All lesions will be rated according to their severity.
5. At terminal sacrifice, in addition to terminal body weight,
the heart, liver, spleen, brain, kidneys (individually),
gcnads (individually), adrenals and thyroid/parathyroid will
be weighed to three significant figures. Organ weight to
body weight ratios will be computed.
G, Statistical Procedures:
In general, the data will be examined using analysis of variance
techniques followed by a multiple comparison procedure for detecting
differences between pairs of means. Some anatomical and clinical
pathology data may require nonparametric techniques to aid in
interpretation.
H. Data Collections and Reporting:
Abnormal observations, body weights, feed consumptions, dose
formulation documentation, and general study comments will be
recorded in bound laboratory notebooks. Clinical laboratory data
will be recorded in bound notebooks or will be direct instrument
or computer output. Pathology data, including organ weights,
will be recorded on individual loose-leaf pathology sheets (one
per animal). At the completion of the study, all data and specimens
will be transferred to the Quality Assurance Unit for storage in
the test laboratory archives.
The following data will be collected and included in the final report:
o Sections on introduction, materials and methods, conclusions and
discussion
o Results of all chemical analyses
o Abnormal appearance or behavior
o Individual and mean body weights initially and weekly through
13 weeks
o Results of the ophthalmological examination
G - 11
10 .
-------
Experiment Number 5221.06
o Individual and mean hematology, bleed chemistry and urinalysis
as outlined.
o Individual and mean organ weights (heart, liver, spleen, brain,
kidneys, gonads, adrenals, and thyroid/parathyroid) from all
animals at termination
o Individual necropsy observations of all animals
o Individual histopathology of tissues as outlined.
XI. RECORDS TO BE MAINTAINED •
All raw data pertaining to the conduct of this study including the
final report will be retained as the regulations require in the archives
at Microbiological Associates Inc., 5221 River Road, Bethesda, MD
20816. If at some time in the future any of these data are to bs
discarded, the sponsor will be first notified to obtain periirdssicn.
XII. STANDARD OPERATION PROCEDURES AND PROTOCOL ALTERATION
All procedures not specified in this protocol will be performed in
accordance with the Microbiological Associates Inc. Standard Operating
Procedures' Manual and in compliance with the FDA's Good Laboratory
Practice Regulations.
Alterations of the study tray be made after the study has been initiated.
In the event that the sponsor verbally authorizes a change in protocol,
such change will be honored by Microbiological Associates Inc. However,
it is then the responsibility of the sponsor to produce written
verification of the verbal authorization, which will result in the
issuance of an official protocol amendment.
XIII. REPONSIBILTTTES
1. L.T, Mulligan, Ph.D: Principal Investigator/Study Director
2. Barry S-. Levins, D.Sc., D.A.B.T.: Toxicologist
3. Lucas H. Brennecke, V.M.D., Ph.D.: Veterinary Pathologist
4. John Miller, DVM, AGLAM: Laboratory Animal Veterinarian
5. Harold J. Paulin, M.S., Chemist
6. Jean L. Causer, B.S.: Operations Supervisor
7, Nona S. Karten, M.A.: Quality Assurance
G - 12
11
-------
Experiment Number 5221.06
XIV. REFERENCES
1. "Guidelines for Carcinogen Bioassay in Small Rodents", Sontag,
J.M., Page, N.P., and Saffiotti, U., NCI, DHEW Publication No.
(NIH) 78-801.
2. Contract with Research Triangle Institute.
L.T. Mulligan) Ph.D. '
Principal Investigator
Sponsor
-? SC-l •
' ^'ifi
Date
Date
G - 13
12
-------
mCTQCQL AMENDMENT
ORIGINAL
Date: July 24, 1936
Study No.; 5221.06
Title; Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Eats
Amendment:
18. Page 8, Part X, Section D;
Delete "and biomicroscopic (slitlaitp)".
Reason: Incorrect in protocol; it was never intended to be done by the
ophthalmologist.
Study(Director//Dat
Sponsor Approval ^~"^ Date
X; MICROBIOLOGICAL
ASSOCIATES INC.
-------
PRC'IOCOL AMENDMENT
OR G NA!
Date: July 24, 1986
Study No.: 5221.06
Title: Subchronic Toxicity of Ortha-Cresol in Sprague Dawley Rats
Amendment;
17. Page 6, Part X, Section A, No. 3:
"for a total period of 13 weeks" should read "for a period of thirteen
weeks or until sacrifice,
Reason: Required due to staggered sacrifice schedule.
Sponsor Approval
/Date1
°l
te
G - 15
MICROBIOLOGICAL
ASSOCIATES INC.
-------
PROTOCOL AMENDMENT
OR G M/
Date: July 24, 1986
Study No.: 5221.06
Title; Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
Amendment:
16. The interim sacrifice was conducted over a two-day period (test days 46
and 47), and the terminal sacrifice was conducted over a three-day period
(test days 92, 93 and 94).
Reason: The large number of animals in the study did not allow
necropsies and clinical pathology evaluations to be conducted in one day
at either the interim or terminal sacrifice.
Study Director / /Date
Sponsor Approval Date
MICROBIOLOGICAL
ASSOCIATES INC.
-------
Experiment Number 5221.06
PROTOCOL AKENTMENT
Date: September 13, 1985
Study Number: 5221.06
Title; Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
Mendment:
1. Page 1 Part III Section A Scheduled Initiation Date: 16 September 1985.
Section B Proposed Termination Date: 16 December 1985.
Reason: Delay in start due to original animals being found unhealthy.
2. Page 4 Part V Section A No. 4 Supplier: Charles River Breeding Laboratories
lakeview, NY
Reason: Source not stated in protocol.
3. Page 5 -Part VIII Section A: Add the following sentence at the end.
"Animals were group housed during the quarnatine
period but individually housed at test animal
section."
Reason: Omitted in protocol.
4. Page 6 Part X Section A No. 6: Dosing solutions will not be refrigerated.
Reason: Refrigeration not necessary and may cause the test article to come
out of solution.
Dose levels
5. Page 7 Part X Section B Treatment Groups: Group fmq/kq/davl
2 50
3 175
4 ' 600
Reason: Not stated in protocol.
17
-------
Experiment Number 5221.06
6. Page 7 Part X Section C No.2: Clinical Observations: Change "examined
• weekly" to "examined daily."
Reason: Incorrect in protocol.
7. Page 8 Part X Section C No. 5; The following senctence is to be deleted
from the protocol. "An estimate of the
mg of test material consumed/body
weight/day will then be calculated."
Reason; Not a diet study.
8. Page 10 Part X Section H Data Collections and Reporting: The word "bound"
is deleted from the phrase "bound notebooks,"
Reason: Some notebooks are loose-leaf.
Study Directr / ' Date V
^^
to
Sponsor Approval Date
18
-------
ORIGINAL
PROTOCOL AMENDMENT
Date: Septeiriber 13, 1985
Study Number: 5221.06
Title: Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Bats
Amendment;
1. Page 7, Part X, Section B: _ Treatment Groups: Change 'the phrase
"post-treatment" to "post-treatment initiation" in the first sentence of
the last paragraph.
Reason: Omitted in protocol.
2. Page 7, Part X, Section C, No. 2: Clinical Observations: Change "examined
daily" to "examined weekly."
Reason: Incorrect in protocol.
3. Page 8, Part X, Section E, No. 2: Clinical Pathology: Add Calcium.
Reason: Sponsor request.
Study Direcor
Sponsor Approval Date
G - 19
-------
ORIGINAL
PROTOCOL AMENEMENT
Date: October, 2, 1985
Study Number: 5221.06
Title; Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
fonendment:
4. In anticipation of testing rats for the neurotoxic effects of o-cresol,
3 rats/sex/dose were added on Test Day 1. It was subsequently decided
that a separate experiment to test for these effects "would be performed.
Therefore, these extra animals will be eliminated from study.
5. To facilitate animal identification, ear tags were attached to test
animals. These will be included with necropsy test specimens.
Study Director f , Date
Sponsor Approval Date
G-20
-------
ORIGINAL
PRDIDCOL AMENEMENT
Date: Ocrtober 16," 1985
Study Number: 5221.06
Title: Subchronic Toxieity of Ortho-Cresol in Sprague Dawley Rats
Amendment:
Page 7, Part X, Section B, Treatment Groups: Delete the following sentence.
"The following organs will be weighed: heart, liver, spleen, brain,
kidneys (individually), {jgori5das} (individually), adrenals and thyroid/
parathyroid." O^JMA^S C££t
Reason: Per discussion with the Sponsor, organ weights are not necessary
at the 45-day interim kill.
Page 8, Part X, Section E No, 1: Md prothrombin time (PT) and activated
partial thromboplastin time (APTT), and delete platelet count.
Reason; PT and APTT are better estimates of clotting potential than
platelet count.
Study Director Date
Sponsor Approval Date
G-21
-------
ORIGINAL
PROTOCOL MEMDXENT
Date: November 26," 1985
Study Number: 5221.06
Title: Subchronic Toxicity of Ortho-Cresol in Sprague Dawley Rats
Amendment:
d
9. Page ?, Part VII, Section E, Feed: Substitute "Purina standard lab
chow" with "Purina Rodent Chow No, 5001",
Reason: Omitted in protocol.
10. Page 5, Part VII, Section K, Room Number: change "Room #371" to
"Room #373"
Reason: Incorrect in protocol.
11. Page 5, Part VIII, Quarantine/ Section B: Unusual observations
during the quarantine period can also be reported to the Study Toxicologist.
Reason: Omitted in protocol.
12. Page 9, Part X, Section F, No. 2: If necessary, animals which die on
test are stored in a refrigerator until necropsy but no longer than 16 hours.
Reason: Incorrectly stated as 24 hours in protocol.
13. Page 11, Part XIII, No. 3: Change the Veterinary Pathologist to
Dr. Diana Copeland, Diplomats, ACVP.
Reason: This is necessary to finish all four RTI study reports on time.
Director 1 Date"<•
Sponsor Approval ' Date
G-22
-------
Protocol Deviations Incurred During Conduct of Study 5221.06
9
Date
9/17/85
9/11/85, 12/12/85
9/17/85
9/30/85-10/7/85
Various days
Duration of study
Duration of study
Various days
Various days
Deviation Effect on Study
Baseline serun phosphorus and electrolytes; blood prothroibfn None
time and activoted prothrombin tine were not measured.
Bi microscopic examinations not performed during the Hone
pretreatment and pretermination ophthalmic examinations.
Three animals were stored In the freezer Instead of in None
the refrigerator between the time of death and the tine
of necropsy.
Feeders changed weekly with the exception of week 3 in None
which some were not changed.
Ho documentation was made concerning dosing for two None
females.
No documentation was made concerning the time of day Hone
when dosing was performed.
Ho documentation was made concerning rack, feeder or None
cage bedding changes. . . ,
Animal room temperatures out of recommended range on None
69 days.
Animal room humidity was out of recofmended range on None
27 days.
-------
------- |